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Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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21 pages, 323 KB  
Review
Progress and Recent Developments in HIV Vaccine Research
by Iris Shim, Lily Rogowski and Vishwanath Venketaraman
Vaccines 2025, 13(7), 690; https://doi.org/10.3390/vaccines13070690 - 26 Jun 2025
Cited by 6 | Viewed by 14280
Abstract
Background: Human immunodeficiency virus (HIV) remains a global health challenge despite significant advancements in antiretroviral therapy and prevention strategies. Developing a safe and effective vaccine that protects people worldwide has been a major goal, yet the genetic variability and rapid mutation rate of [...] Read more.
Background: Human immunodeficiency virus (HIV) remains a global health challenge despite significant advancements in antiretroviral therapy and prevention strategies. Developing a safe and effective vaccine that protects people worldwide has been a major goal, yet the genetic variability and rapid mutation rate of the virus continue to pose substantial challenges. Methods: In this review paper, we aim to provide a comprehensive review of previous vaccine candidates and the progress made in HIV vaccine clinical trials, spanning from the late 1990s to 2025. PubMed and ClinicalTrials.gov were searched for English-language Phase 1–3 HIV vaccine trials published from 1990 to March 2025. After de-duplication, titles/abstracts and then full texts were screened; trial phase, regimen, immunogenicity, efficacy, and correlates were extracted into a structured spreadsheet. Owing to platform heterogeneity, findings were synthesized narratively and arranged chronologically to trace the evolution of vaccine strategies. Results: Early vaccine trials demonstrated that a protein subunit vaccine failed to protect against infection, revealing the complexity of HIV evasion strategies and shifting the focus to a comprehensive immune response, including both antibody and T-cell responses. Trials evaluating the role of viral vectors in generating cell-mediated immunity were also insufficient, and suggested that targeting T cell response alone was not enough. In 2009, the RV144 trial made a breakthrough by showing partial protection against HIV infection and providing the first indication of efficacy. This partial success influenced subsequent trials, prompting researchers to further explore the complex immune response required for protection and consider combinations of vaccine technologies to achieve robust, long-lasting immunity. Conclusion: Despite setbacks, decades of rigorous efforts have provided significant contributions to HIV vaccine discovery and development, offering hope for preventing and protecting against HIV infection. The field remains active by continuing to advance our understanding of the virus, refining vaccine strategies, and employing novel technologies. Full article
(This article belongs to the Special Issue Advances in HIV Vaccine Development, 2nd Edition)
15 pages, 2783 KB  
Article
Childhood Immunization Coverage Before, During and After the COVID-19 Pandemic in Italy
by Flavia Pennisi, Andrea Silenzi, Alessia Mammone, Andrea Siddu, Anna Odone, Michela Sabbatucci, Riccardo Orioli, Anna Carole D’Amelio, Francesco Maraglino, Giovanni Rezza and Carlo Signorelli
Vaccines 2025, 13(7), 683; https://doi.org/10.3390/vaccines13070683 - 25 Jun 2025
Cited by 5 | Viewed by 3496
Abstract
Background/Objectives: Maintaining high childhood vaccination coverage is essential to prevent outbreaks of vaccine-preventable diseases. In Italy, Law No. 119/2017 introduced mandatory childhood immunizations, leading to significant improvements. However, the COVID-19 pandemic disrupted routine services, potentially jeopardizing these gains. This study aimed to evaluate [...] Read more.
Background/Objectives: Maintaining high childhood vaccination coverage is essential to prevent outbreaks of vaccine-preventable diseases. In Italy, Law No. 119/2017 introduced mandatory childhood immunizations, leading to significant improvements. However, the COVID-19 pandemic disrupted routine services, potentially jeopardizing these gains. This study aimed to evaluate national and regional trends in vaccine coverage across three phases: post-mandate (2015–2016 vs. 2017–2019), pandemic (2017–2019 vs. 2020–2021), and post-pandemic recovery (2020–2021 vs. 2022–2023). Methods: National and regional administrative data on vaccination coverage at 24 months of age were obtained from the Italian Ministry of Health. Temporal trends were analyzed using Joinpoint regression to estimate annual percent changes (APCs), and absolute changes in coverage (Δ) were calculated across defined periods. Pearson correlation coefficients were used to assess associations between baseline coverage and subsequent changes. Results: After the 2017 mandate, coverage increased significantly for varicella (APC = +28.6%), MenB (+22.6%), and measles (+3.4%). Regionally, varicella coverage rose by up to +58.4% in Emilia-Romagna and measles by +11.1% in Campania. During the pandemic, coverage declined for polio (−2.4% in the South) and measles (−6.2% in Abruzzo), while MenB increased in regions with lower initial uptake (r = −0.918, p < 0.001). Post-pandemic, coverage rebounded, with varicella improving by +20.1% in central regions and measles by +13.9% in Abruzzo. A strong inverse correlation between baseline coverage and improvement was observed for varicella across all periods (r from −0.877 to −0.915). Conclusions: Mandatory vaccination policies led to substantial coverage improvements, and despite the disruption caused by the pandemic, recovery trends were observed for most vaccines. The consistent association between low baseline coverage and stronger gains highlights the resilience of the system, but also the ongoing need for regionally tailored strategies to reduce geographic disparities and ensure equitable immunization across Italy. Full article
(This article belongs to the Section Vaccines and Public Health)
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15 pages, 421 KB  
Review
VITT Pathophysiology: An Update
by Eleonora Petito and Paolo Gresele
Vaccines 2025, 13(6), 650; https://doi.org/10.3390/vaccines13060650 - 17 Jun 2025
Cited by 3 | Viewed by 2956
Abstract
Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare thrombotic disorder first identified in 2021 as a catastrophic syndrome associated with anti-SARS-CoV-2 adenoviral vector (AdV)-vaccine administration. It is characterized by the presence of oligo- or monoclonal anti-PF4 antibodies able to induce in vitro platelet activation [...] Read more.
Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare thrombotic disorder first identified in 2021 as a catastrophic syndrome associated with anti-SARS-CoV-2 adenoviral vector (AdV)-vaccine administration. It is characterized by the presence of oligo- or monoclonal anti-PF4 antibodies able to induce in vitro platelet activation in the presence of PF4. In addition to this immune-based pathomechanism, random splicing events of the Adv-vector DNA encoding for SARS-CoV-2 spike protein resulting in the secretion of soluble spike variants have been postulated as a possible pathophysiological mechanism. More recently, some novel clinical-pathological anti-PF4-associated entities also characterized by thrombosis, thrombocytopenia, and VITT-like antibodies but independent from heparin or AdV-vaccine administration have been identified. To date, these VITT-like disorders have been reported following the administration of vaccines different from anti-SARS-CoV-2 AdV-vaccines, like human papillomavirus (HPV) and mRNA-based COVID-19 vaccines, following a bacterial or viral respiratory infection, and in patients with a monoclonal gammopathy of undetermined significance. The purpose of this review is to provide an update on the knowledge on VITT pathogenesis, focusing on recent findings on anti-PF4 antibodies, on a possible genetic predisposition to VITT, on VITT-antibody intracellular activated pathways, on lipid metabolism alterations, and on new VITT-like disorders. Full article
(This article belongs to the Special Issue Vaccine-Induced Immune Thrombotic Thrombocytopenia)
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17 pages, 312 KB  
Review
Human Alpha Herpesviruses Infections (HSV1, HSV2, and VZV), Alzheimer’s Disease, and the Potential Benefits of Targeted Treatment or Vaccination—A Virological Perspective
by Peter A. C. Maple and Akram A. Hosseini
Vaccines 2025, 13(6), 572; https://doi.org/10.3390/vaccines13060572 - 27 May 2025
Cited by 5 | Viewed by 6646
Abstract
Understanding the contribution of human herpesviruses to the aetiology of neurodegenerative diseases is an emerging field of interest. The association of Epstein–Barr virus with multiple sclerosis is the most researched example; however, the definitive proof of causation is still lacking. Alzheimer’s disease (AD) [...] Read more.
Understanding the contribution of human herpesviruses to the aetiology of neurodegenerative diseases is an emerging field of interest. The association of Epstein–Barr virus with multiple sclerosis is the most researched example; however, the definitive proof of causation is still lacking. Alzheimer’s disease (AD) is the most common form of dementia and typically manifests in individuals aged over 65 years; however, it also occurs in a small number of individuals aged less than 65 years. A combination of environmental, genetic, and lifestyle factors is believed to contribute to the development of AD. There have been several reports describing potential associations of infections or reactivations of human alphaherpesviruses with AD. A particular characteristic of human alphaherpesviruses (herpes simplex viruses 1 and 2, varicella zoster virus) is that they are neurotropic and that lifelong infection (latency) is established mainly in the dorsal root and trigeminal ganglia. There have also been reports that suppression of alphaherpesvirus infections through either vaccination or the application of antiviral treatments may be protective against the development of AD. Zoster vaccines and acyclovir may prove to be effective interventions for preventing or limiting the progression of AD. This is particularly relevant as there are currently no available cheap and effective treatments for AD. In this review, the basic virology of human alphaherpesviruses is described followed by their epidemiology and associations with AD. Finally, the prevention and treatment of human alphaherpesviruses are considered in the context of potential applications for the prevention of AD. Full article
(This article belongs to the Special Issue Varicella and Zoster Vaccination)
16 pages, 7103 KB  
Article
Adjuvanted RNA Origami—A Tunable Peptide Assembly Platform for Constructing Cancer Nanovaccines
by Theresa Yip, Xinyi Tu, Xiaodong Qi, Hao Yan and Yung Chang
Vaccines 2025, 13(6), 560; https://doi.org/10.3390/vaccines13060560 - 25 May 2025
Cited by 4 | Viewed by 2528
Abstract
Background/Objectives: Cancer peptide vaccines represent a promising strategy to develop targeted and personalized treatments for cancer patients. While tumor peptides alone are insufficient in mounting effective immune responses, the addition of adjuvants can enhance their immunogenicity. Nanoparticle delivery systems have been explored as [...] Read more.
Background/Objectives: Cancer peptide vaccines represent a promising strategy to develop targeted and personalized treatments for cancer patients. While tumor peptides alone are insufficient in mounting effective immune responses, the addition of adjuvants can enhance their immunogenicity. Nanoparticle delivery systems have been explored as vaccine carriers to incorporate both adjuvants and peptides. One such nanoparticle is RNA origami (RNA-OG), a nucleic acid nanostructure that is programmed to form different sizes and shapes. Our designed RNA-OG can incorporate various biomolecules and has intrinsic adjuvant activity by acting as a toll-like receptor 3 agonist. We previously showed that the RNA-OG functions as an adjuvanted, carrier-free vaccine platform to assemble peptides. Although effective, only a fixed number of peptides (13) could be covalently linked to each RNA-OG. Methods: Here, we developed a simple physical assembly strategy to attach polylysine-linked neopeptides onto RNA-OG so that the number of peptides per RNA-OG could be readily tuned and tested for their immunogenicity. Results: Although the vaccines with a high number of peptides, i.e., 100–200 peptides/RNA-OG, led to greater peptide presentation by bone marrow-derived dendritic cells, they failed to mount effective CD8+ T cell responses against engrafted tumor cells, probably owing to an induction of early T cell exhaustion. Interestingly, the same vaccine format with a low number of peptides, i.e., 10–15 peptides/RNA-OG, enhanced CD8+ T cell responses without provoking T cell exhaustion in tumor-bearing mice, leading to strong protective anti-tumor immunity. In comparison, the covalently assembled RNA-OG-peptide vaccine, having a similarly low peptide dosage, offered the highest therapeutic efficacy. Thus, our RNA-OG nanostructure provides a simple and tunable platform for peptide loading to optimize vaccine efficacy. Conclusions: Our findings have significant implications for peptide vaccine design regarding peptide dosages and structural stability of RNA-OG complexed with peptides, which could guide the development of more effective peptide vaccines for cancer immunotherapy. Full article
(This article belongs to the Special Issue Novel Immunotherapies, Cell Therapies and Cancer Vaccines)
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22 pages, 5356 KB  
Article
Mucosal and Serum Neutralization Immune Responses Elicited by COVID-19 mRNA Vaccination in Vaccinated and Breakthrough-Infection Individuals: A Longitudinal Study from Louisville Cohort
by Lalit Batra, Divyasha Saxena, Triparna Poddar, Maryam Zahin, Alok Amraotkar, Megan M. Bezold, Kathleen T. Kitterman, Kailyn A. Deitz, Amanda B. Lasnik, Rachel J. Keith, Aruni Bhatnagar, Maiying Kong, Jon D. Gabbard, William E. Severson and Kenneth E. Palmer
Vaccines 2025, 13(6), 559; https://doi.org/10.3390/vaccines13060559 - 24 May 2025
Cited by 4 | Viewed by 2169
Abstract
Background/Objectives: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has resulted in 777 million cases worldwide. Various vaccines have been approved to control the spread of COVID-19, with mRNA vaccines (Pfizer and Moderna) being widely used in the [...] Read more.
Background/Objectives: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has resulted in 777 million cases worldwide. Various vaccines have been approved to control the spread of COVID-19, with mRNA vaccines (Pfizer and Moderna) being widely used in the USA. We conducted a prospective longitudinal study to analyze the immune response elicited by two/three and four doses of monovalent mRNA vaccines in both vaccinated individuals and those who experienced breakthrough infections. Participants were stratified into different age groups: 18–40, 41–60, and over 60 years. Methods: We assessed cross-variant neutralization responses in two cohorts—Cohort I: n = 167 (serum), Cohort II: n = 92 (serum and nasal swab) samples—using infectious virus microneutralization assay (MN) and antibody (IgG or IgA) binding ELISA titers to the spike protein receptor binding domain (RBD). Samples were collected from the Louisville Metro–Jefferson County Co-Immunity Project, a federally funded, population-based study for the surveillance of SARS-CoV-2 in Jefferson County, Kentucky during 2020–2022, involving both health care workers and a local community. Results: Individuals who received two doses of the mRNA vaccine exhibited reduced neutralization against Beta, Delta, and Omicron BA.1 variants compared to wildtype Wuhan, with further decline observed six months post-booster vaccination. However, individuals who experienced natural COVID-19 infection (breakthrough) after receiving two vaccine doses showed enhanced neutralization and antibody responses, particularly against Omicron BA.1. Following the 3rd dose, antibodies and neutralization responses were restored. Among triple-vaccinated individuals, reduced neutralization was observed against Omicron variants BA.1, BA.5, and BA.2 compared to Wuhan. Neutralization responses were better against BA.2 variant compared to BA.1 and BA.5. However, individuals who received three doses of vaccine and experienced a breakthrough infection (n = 45) elicited significantly higher neutralizing antibodies responses against all Omicron subvariants compared to vaccinated individuals. Interestingly, nasal swab samples collected from volunteers with breakthrough infection showed significantly elevated spike-reactive mucosal IgA antibodies and enhanced cross neutralization against BA.1, BA.2, and BA.5 compared to individuals who received only three vaccine doses. Conclusions: mRNA vaccination elicits a strong systemic immune response by boosting serum neutralizing antibodies (NAb), although this protection wanes over time, allowing new variants to escape neutralization. Breakthrough individuals have extra enrichment in nasal NAb offering protection against emerging variants. This longitudinal immune profiling underscores the strengthening of pandemic preparedness and supports the development of durable mucosal vaccines against respiratory infectious disease. Full article
(This article belongs to the Special Issue Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development: 2nd Edition)
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20 pages, 986 KB  
Review
Past, Present, and Future of Viral Vector Vaccine Platforms: A Comprehensive Review
by Justin Tang, Md Al Amin and Jian L. Campian
Vaccines 2025, 13(5), 524; https://doi.org/10.3390/vaccines13050524 - 15 May 2025
Cited by 20 | Viewed by 10848
Abstract
Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often [...] Read more.
Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often superior to what traditional inactivated or subunit vaccines can achieve. This has accelerated their application to a wide array of pathogens and disease targets, from well-established threats like HIV and malaria to emerging infections such as Ebola, Zika, and SARS-CoV-2. The COVID-19 pandemic further highlighted the agility of viral vector platforms, with several adenovirus-based vaccines quickly authorized and deployed on a global scale. Despite these advances, significant challenges remain. One major hurdle is pre-existing immunity against commonly used vector backbones, which can blunt vaccine immunogenicity. Rare but serious adverse events, including vector-associated inflammatory responses and conditions like vaccine-induced immune thrombotic thrombocytopenia (VITT), have raised important safety considerations. Additionally, scaling up manufacturing, ensuring consistency in large-scale production, meeting rigorous regulatory standards, and maintaining equitable global access to these vaccines present profound logistical and ethical dilemmas. In response to these challenges, the field is evolving rapidly. Sophisticated engineering strategies, such as integrase-defective lentiviral vectors, insect-specific flaviviruses, chimeric capsids to evade neutralizing antibodies, and plug-and-play self-amplifying RNA approaches, seek to bolster safety, enhance immunogenicity, circumvent pre-existing immunity, and streamline production. Lessons learned from the COVID-19 pandemic and prior outbreaks are guiding the development of platform-based approaches designed for rapid deployment during future public health emergencies. This review provides an exhaustive, in-depth examination of the historical evolution, immunobiological principles, current platforms, manufacturing complexities, regulatory frameworks, known safety issues, and future directions for viral vector-based vaccines. Full article
(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)
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24 pages, 592 KB  
Review
Addressing the Underestimated Burden of RSV in Older Adults in Europe: Epidemiology, Surveillance Gaps, and Public Health Implications
by Floriana D’Ambrosio, Marta Lomazzi, Michael Moore, Ada Maida, Roberto Ricciardi, Ludovica Munno, Monia Lettieri, Elisabetta De Vito, Walter Ricciardi and Giovanna Elisa Calabrò
Vaccines 2025, 13(5), 510; https://doi.org/10.3390/vaccines13050510 - 12 May 2025
Cited by 8 | Viewed by 6695
Abstract
Background/Objectives: Respiratory Syncytial Virus (RSV) is a leading cause of Lower Respiratory Tract Infections (LRTIs), posing a serious threat to vulnerable populations. Although growing evidence highlights its significant impact on older adults, RSV surveillance and data collection remain largely focused on children, underestimating [...] Read more.
Background/Objectives: Respiratory Syncytial Virus (RSV) is a leading cause of Lower Respiratory Tract Infections (LRTIs), posing a serious threat to vulnerable populations. Although growing evidence highlights its significant impact on older adults, RSV surveillance and data collection remain largely focused on children, underestimating the burden in older and high-risk adults. This review aims to synthesize current evidence on the epidemiological and clinical impact of RSV in older adults in Europe, assess existing surveillance strategies, and identify gaps to guide targeted public health responses. Methods: A two-phase research strategy was adopted. First, a comprehensive review of studies published between 2015–2025 was conducted via PubMed, focusing on the RSV burden in high-risk and elderly populations in Europe. Second, a structured web screening was performed to assess the status of existing RSV surveillance systems, focusing on eight selected European countries. Results: The review reported RSV prevalence rates ranging from 1% to 64.7% among older adults, with a high prevalence of comorbidities that exacerbate disease severity. Hospitalization rates varied between 12.6–55.9%, while mortality ranged from 2.15% to 13%, reaching up to 36% in intensive care settings. Surveillance systems for adult RSV infections across Europe remain limited and fragmented, with only 37.5% (3/8) of analyzed countries having dedicated surveillance for adults. Conclusions: RSV represents a substantial and underrecognized threat to older adults, with significant clinical and healthcare implications. Strengthening surveillance, standardizing data collection, and ensuring equitable access to newly available preventive measures are urgent priorities to reduce the disease burden, protect vulnerable populations, and support resilient health systems against future health challenges. Full article
(This article belongs to the Special Issue Respiratory Syncytial Virus (RSV) Vaccine)
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13 pages, 231 KB  
Review
Dengue Vaccine Development and Deployment into Routine Immunization
by Annelies Wilder-Smith, Thomas Cherian and Joachim Hombach
Vaccines 2025, 13(5), 483; https://doi.org/10.3390/vaccines13050483 - 29 Apr 2025
Cited by 10 | Viewed by 7616
Abstract
Dengue has emerged as a significant global health threat. Despite decades of research, only two dengue vaccines—CYD-TDV (Dengvaxia) and TAK-003 (Qdenga)—have been licensed to date, with limited implementation. This paper explores and outlines strategies for integrating dengue vaccines into routine immunization programs, particularly [...] Read more.
Dengue has emerged as a significant global health threat. Despite decades of research, only two dengue vaccines—CYD-TDV (Dengvaxia) and TAK-003 (Qdenga)—have been licensed to date, with limited implementation. This paper explores and outlines strategies for integrating dengue vaccines into routine immunization programs, particularly in high-burden regions. TAK-003, a tetravalent live-attenuated vaccine, has demonstrated 61% efficacy against virologically confirmed dengue and 84% efficacy against hospitalizations in endemic settings. However, concerns remain about vaccine-enhanced disease, particularly among seronegative individuals exposed to DENV3 and DENV4. WHO recommends targeted introduction in high-transmission settings without pre-vaccination screening, while ongoing post-introduction studies will further clarify long-term safety and efficacy. Effective vaccine rollout requires a multi-pronged approach, including school-based immunization, integration with adolescent health services, and strong community engagement. Decision-making for vaccine introduction should be guided by National Immunization Technical Advisory Groups (NITAGs), local epidemiological data, and cost-effectiveness assessments. While future vaccines, including mRNA and virus-like particle candidates, are under development, optimizing the use of currently available vaccines is crucial to reducing dengue’s public health impact. Given the continued rise in cases, immediate action—combining vaccination with vector control—is essential to prevent further morbidity and mortality. Full article
(This article belongs to the Special Issue 50 Years of Immunization—Steps Forward)
19 pages, 3320 KB  
Article
Generation of Chimeric African Swine Fever Viruses Through In Vitro and In Vivo Intergenotypic Gene Complementation
by Tomoya Kitamura, Kentaro Masujin, Mitsutaka Ikezawa, Aruna Ambagala and Takehiro Kokuho
Vaccines 2025, 13(5), 462; https://doi.org/10.3390/vaccines13050462 - 25 Apr 2025
Cited by 7 | Viewed by 2445
Abstract
Background/Objectives: African swine fever (ASF), a fatal febrile hemorrhagic disease in domestic pigs and Eurasian wild boars, is caused by ASF virus (ASFV). ASF continues to spread across the globe, causing a significant impact on the world’s pig industry. Recently, highly virulent [...] Read more.
Background/Objectives: African swine fever (ASF), a fatal febrile hemorrhagic disease in domestic pigs and Eurasian wild boars, is caused by ASF virus (ASFV). ASF continues to spread across the globe, causing a significant impact on the world’s pig industry. Recently, highly virulent chimeric ASFV (chASFV) strains with recombined genomes of the p72 genotype I and II viruses have been reported in China, Vietnam and Russia. Methods: In order to understand the propensity of ASFV genome for recombination, we attempted to experimentally generate chASFVs both in vitro and in vivo employing two distinct attenuated ASFV strains: OUR T88/3 (genotype I) and AQSΔB119L (genotype II). Results: When IPKM cells were co-infected with ASFV OUR T88/3 and AQSΔB119L strains, three genetically distinct chASFV emerged. When pigs were inoculated with the individual chASFV isolates, all pigs developed acute ASF. When four pigs were co-infected with ASFV OUR T88/3 and AQSΔB119L, all of them developed acute ASF and died or were euthanized. Three chASFV strains were successfully isolated from splenic homogenates from each pig. Conclusions: Our research indicates that genotype I and II chASFV with diverse genomes can be easily generated experimentally both in vitro and in vivo. Full article
(This article belongs to the Section Veterinary Vaccines)
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22 pages, 723 KB  
Review
From Antibodies to Immunity: Assessing Correlates of Flavivirus Protection and Cross-Reactivity
by Hannah E. Flores, Eduar Fernando Pinzon Burgos, Sigrid Camacho Ortega, Alonso Heredia and Joel V. Chua
Vaccines 2025, 13(5), 449; https://doi.org/10.3390/vaccines13050449 - 24 Apr 2025
Cited by 3 | Viewed by 4370
Abstract
Flaviviruses are arthropod-borne RNA viruses that can cause a wide range of human diseases, from mild symptoms to severe illness with multiorgan failure and death. Effective prevention of these diseases relies on identifying reliable vaccine targets, typically measured by correlates of protection (CoPs), [...] Read more.
Flaviviruses are arthropod-borne RNA viruses that can cause a wide range of human diseases, from mild symptoms to severe illness with multiorgan failure and death. Effective prevention of these diseases relies on identifying reliable vaccine targets, typically measured by correlates of protection (CoPs), which help indicate host immunity after vaccination. Current vaccines primarily focus on neutralizing antibodies (nAbs) against the viral envelope E protein, though emerging evidence suggests other potential targets may also be effective in disease prevention. Additionally, there is growing evidence of cross-protection between different flaviviruses when immunity to one virus is achieved, although this can be limited by antibody-dependent enhancement. This review examines the current understanding of flavivirus immunity, CoPs, and the potential for cross-protection in the context of existing vaccine strategies. Full article
(This article belongs to the Special Issue Vaccines Against Flaviviruses and Alphaviruses: Recent Advances and Future Challenges—2nd Edition)
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19 pages, 689 KB  
Review
Maternal Immunization: Current Evidence, Progress, and Challenges
by Veronica Santilli, Mayla Sgrulletti, Giorgio Costagliola, Alessandra Beni, Maria Felicia Mastrototaro, Davide Montin, Caterina Rizzo, Baldassarre Martire, Michele Miraglia del Giudice and Viviana Moschese
Vaccines 2025, 13(5), 450; https://doi.org/10.3390/vaccines13050450 - 24 Apr 2025
Cited by 12 | Viewed by 10474
Abstract
Maternal immunization is a key strategy for protecting pregnant individuals and newborns from infectious diseases. This review examines the mechanisms and benefits of maternal immunization, with a focus on transplacental IgG transfer and immune system interactions. We provide an overview of current recommendations [...] Read more.
Maternal immunization is a key strategy for protecting pregnant individuals and newborns from infectious diseases. This review examines the mechanisms and benefits of maternal immunization, with a focus on transplacental IgG transfer and immune system interactions. We provide an overview of current recommendations and the safety and efficacy profiles of maternal vaccines, including influenza, tetanus–diphtheria–acellular pertussis (Tdap), respiratory syncytial virus (RSV), COVID-19, and hepatitis B. Additionally, we analyze the barriers to maternal immunization, such as misinformation, vaccine hesitancy, and disparities in healthcare access, while exploring potential strategies to overcome these challenges through targeted educational initiatives, improved provider communication, and policy-driven interventions aimed at increasing vaccine confidence and accessibility. Finally, this review highlights recent innovations and future directions in maternal immunization, including emerging vaccines for Group B Streptococcus and cytomegalovirus. Expanding immunization programs and advancing research on maternal–fetal immunity are essential to optimizing vaccination strategies, improving public health outcomes, and reducing the global burden of infectious diseases. Full article
(This article belongs to the Special Issue Vaccines for the Vulnerable Population)
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27 pages, 819 KB  
Review
HPV Vaccine Delivery Strategies to Reach Out-of-School Girls in Low- and Middle-Income Countries: A Narrative Review
by Erica N. Rosser, Megan D. Wysong, Joseph G. Rosen, Rupali J. Limaye and Soim Park
Vaccines 2025, 13(5), 433; https://doi.org/10.3390/vaccines13050433 - 22 Apr 2025
Cited by 5 | Viewed by 5059
Abstract
Background/Objectives: Low- and middle-income countries (LMICs) have the highest global burden of cervical cancer deaths. Human papillomavirus (HPV) vaccination is a key strategy for cervical cancer elimination, and in LMICs, global recommendations to vaccinate girls aged 9–14 years against HPV are generally implemented [...] Read more.
Background/Objectives: Low- and middle-income countries (LMICs) have the highest global burden of cervical cancer deaths. Human papillomavirus (HPV) vaccination is a key strategy for cervical cancer elimination, and in LMICs, global recommendations to vaccinate girls aged 9–14 years against HPV are generally implemented through school-based immunization platforms. Unfortunately, this strategy risks missing out-of-school (OOS) girls (i.e., girls not enrolled in formal schools). This narrative review maps the literature and synthesizes existing evidence on service delivery strategies for reaching OOS girls with HPV vaccination in LMICs. Methods: Using relevant databases, we conducted a narrative review of published, peer-reviewed literature to map and synthesize the existing evidence on effective service delivery strategies for reaching OOS girls with HPV vaccination in LMICs. Results: The 21 articles identified presented findings on strategies to reach OOS girls, with the most frequently cited strategies being facility-based and community outreach approaches. Authors also described community-based strategies used to identify and enumerate OOS girls, including peer tracing, church outreach initiatives, as well as partnerships with local groups (e.g., civil service organizations) and individuals (e.g., healthcare workers, teachers). The articles discussed barriers at the individual (e.g., lack of parental consent), facility/program delivery (e.g., lack of transportation for vaccines), and community (e.g., distance from homes to vaccination services) levels to HPV vaccine delivery, as well as solutions at the facility/program delivery (e.g., pilot programs) and community (e.g., multi-level partnerships) levels. Conclusions: Additional research is needed to evaluate implementation strategies targeting OOS girls with HPV vaccination. A better understanding of these strategies can provide valuable insights for HPV vaccine policymakers, healthcare providers, and program implementers. Full article
(This article belongs to the Special Issue Prevention of Human Papillomavirus (HPV) and Vaccination)
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12 pages, 1557 KB  
Article
Neutralizing Antibody Response to the AreXvy Respiratory Syncytial Virus Vaccine in Lung Transplant Recipients: Assessment Against Reference and Seasonal Strains
by Liran Levy, Dafna Yahav, Mark Benzimra, Yael Bezalel, Tomer Hoffman, Neta Shirin, Tomer Sinai, Menucha Jurkowicz, Ofir Deri, Noa Matalon, Milton Saute, Yaniv Lustig, Eyal Nachum, Michael Peled, Ital Nemet and Michal Mandelboim
Vaccines 2025, 13(4), 398; https://doi.org/10.3390/vaccines13040398 - 11 Apr 2025
Cited by 4 | Viewed by 2614
Abstract
Background: Respiratory Syncytial Virus (RSV) is a significant cause of morbidity and mortality among lung transplant (LTx) recipients. Therapeutic options are limited, emphasizing the importance of prevention. The Arexvy® vaccine (RSVPreF3) showed promising efficacy among immunocompetent adults; however, data on its immunogenicity [...] Read more.
Background: Respiratory Syncytial Virus (RSV) is a significant cause of morbidity and mortality among lung transplant (LTx) recipients. Therapeutic options are limited, emphasizing the importance of prevention. The Arexvy® vaccine (RSVPreF3) showed promising efficacy among immunocompetent adults; however, data on its immunogenicity in solid organ transplant recipients remain unclear. Methods: A single-center retrospective cohort study, including all LTx recipients who were vaccinated with Arexvy in February 2024. Baseline and follow-up serum samples (1, 3, and 6 months post-vaccination) were analyzed for antibody responses using a commercial RSV ELISA kit and micro-neutralization assays against historical reference RSV A/B ATCC strains and seasonal RSV strains. Adverse events were documented. Results: A total of 28 recipients received the vaccine. Twenty-one (75%) were male, and the median age was 62 years (interquartile range [IQR], 53–67). The median time from transplant was 486 days (IQR, 243–966). Vaccination elicited strong immunogenic responses, demonstrating a twofold increase in ELISA-determined antibody levels at one month post-vaccination, which were sustained for six months. At one month, 67% of recipients had antibody levels exceeding the cutoff threshold. Micro-neutralization assays showed a significant increase in neutralizing antibodies against all tested variants (RSV A/B ATCC and seasonal RSV A/B), with titers remaining at least twofold higher than pre-vaccination levels. No serious adverse events were observed. Conclusions: Our findings demonstrate a sustained antibody response to the Arexvy® vaccine in a cohort of LTx recipients, with antibody titers sustained over six months. Further research is needed to assess the long-term durability of the immune response and the potential immunogenicity of this vaccine in LTx populations. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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17 pages, 267 KB  
Review
The Application of mRNA Technology for Vaccine Production—Current State of Knowledge
by Anna Paczkowska, Karolina Hoffmann, Agata Andrzejczak, Weronika Faustyna Pucek, Dorota Kopciuch, Wiesław Bryl, Elżbieta Nowakowska and Krzysztof Kus
Vaccines 2025, 13(4), 389; https://doi.org/10.3390/vaccines13040389 - 4 Apr 2025
Cited by 5 | Viewed by 6209
Abstract
Over the past 20 years, intensive research has been conducted on the development of therapeutic mRNA, leading to numerous discoveries that have enabled its use in therapy. The main achievements in this field include increasing mRNA stability, reducing its immunogenicity (i.e., its ability [...] Read more.
Over the past 20 years, intensive research has been conducted on the development of therapeutic mRNA, leading to numerous discoveries that have enabled its use in therapy. The main achievements in this field include increasing mRNA stability, reducing its immunogenicity (i.e., its ability to trigger an immune response), and solving the challenge of delivering mRNA into cells—all to achieve a therapeutic effect. The aim of this study was to review the scientific literature on the use of mRNA technology in the production of vaccines. Various methods of applying mRNA technology that could potentially be introduced into clinical practice in the future are described. A detailed analysis was conducted on the approved COVID-19 vaccines developed by Pfizer/BioNTech (New York, NY, USA) and Moderna (Kirkland, QC, Canada), as their introduction marked a groundbreaking moment in the advancement of mRNA technology. This study was based on the latest scientific literature from reputable publishers and medical databases such as PubMed and ClinicalTrials. In conclusion, mRNA technology is currently experiencing rapid development, significantly driven by the ongoing COVID-19 pandemic. The application of this technology holds great potential not only for vaccines against infectious diseases but also for cancer treatment. However, further research is necessary to facilitate its broader clinical implementation. Full article
(This article belongs to the Special Issue Vaccine Development and Global Health)
25 pages, 1446 KB  
Review
Exploring CD169+ Macrophages as Key Targets for Vaccination and Therapeutic Interventions
by Rianne G. Bouma, Aru Z. Wang and Joke M. M. den Haan
Vaccines 2025, 13(3), 330; https://doi.org/10.3390/vaccines13030330 - 20 Mar 2025
Cited by 6 | Viewed by 5513
Abstract
CD169 is a sialic acid-binding immunoglobulin-like lectin (Siglec-1, sialoadhesin) that is expressed by subsets of tissue-resident macrophages and circulating monocytes. This receptor interacts with α2,3-linked Neu5Ac on glycoproteins as well as glycolipids present on the surface of immune cells and pathogens. CD169-expressing macrophages [...] Read more.
CD169 is a sialic acid-binding immunoglobulin-like lectin (Siglec-1, sialoadhesin) that is expressed by subsets of tissue-resident macrophages and circulating monocytes. This receptor interacts with α2,3-linked Neu5Ac on glycoproteins as well as glycolipids present on the surface of immune cells and pathogens. CD169-expressing macrophages exert tissue-specific homeostatic functions, but they also have opposing effects on the immune response. CD169+ macrophages act as a pathogen filter, protect against infectious diseases, and enhance adaptive immunity, but at the same time pathogens also exploit them to enable further dissemination. In cancer, CD169+ macrophages in tumor-draining lymph nodes are correlated with better clinical outcomes. In inflammatory diseases, CD169 expression is upregulated on monocytes and on monocyte-derived macrophages and this correlates with the disease state. Given their role in promoting adaptive immunity, CD169+ macrophages are currently investigated as targets for vaccination strategies against cancer. In this review, we describe the studies investigating the importance of CD169 and CD169+ macrophages in several disease settings and the vaccination strategies currently under investigation. Full article
(This article belongs to the Special Issue Vaccines Targeting Dendritic Cells)
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27 pages, 2149 KB  
Article
Inflammatory and Humoral Immune Responses to Commercial Autogenous Salmonella Bacterin Vaccines in Light-Brown Leghorn Pullets: Primary and Secondary Vaccine Responses
by Chrysta N. Beck, Jossie M. Santamaria and Gisela F. Erf
Vaccines 2025, 13(3), 311; https://doi.org/10.3390/vaccines13030311 - 13 Mar 2025
Cited by 3 | Viewed by 1775
Abstract
Background/Objectives: Commercial poultry flocks undergo Salmonella vaccinations to manage salmonellosis outbreaks. Due to reports of severe injection site reactions to Salmonella bacterins, assessment of local inflammatory responses is necessary. The objective was to assess local inflammatory and systemic humoral immune responses to commercial [...] Read more.
Background/Objectives: Commercial poultry flocks undergo Salmonella vaccinations to manage salmonellosis outbreaks. Due to reports of severe injection site reactions to Salmonella bacterins, assessment of local inflammatory responses is necessary. The objective was to assess local inflammatory and systemic humoral immune responses to commercial autogenous Salmonella bacterin vaccines (SV1 or SV2) following primary or secondary intradermal (i.d.) vaccination in Light-Brown Leghorns (LBLs). Methods: LBL pullets received primary (14 wks) or secondary (19 wks) vaccination by i.d. growing feather (GF) pulp injection of SV1, SV2, Salmonella Enteritidis (SE) lipopolysaccharide (LPS), or water–oil–water emulsion (V). Local leukocyte levels and relative cytokine mRNA expression were monitored before (0 d) and at 6 h, 1 d, 2 d, 3 d, 5 d, and 7 d post-GF pulp injection (p.i.). Blood was collected through 28 d post-primary or -secondary vaccination, and SE-specific antibodies were quantified via ELISA. Results: Primary vaccine administration increased local heterophil and macrophage levels and increased IL-6 and IL-8 mRNA expressions at 6 h p.i., independent of treatment. Secondary administration extended these local immune activities through 3 d p.i. and included prolonged IL-17A mRNA expression. Primary and secondary GF-pulp injection with V resulted in rapid lymphocyte recruitment by 6 h p.i., comprised primarily of CD4+ and γδ T cells. SV1 and SV2 also produced a T-dependent systemic humoral immune response, as indicated by the IgM-to-IgG isotype switch, along with a memory phenotype in the secondary response. Conclusions: These commercial-killed Salmonella vaccines, when prepared in water–oil–water emulsions, stimulated prolonged innate and T helper (Th) 17-type inflammatory responses at the injection site and produced a classic systemic humoral immune response after a second vaccination. Further research is needed to determine if extended inflammation influences adaptive immune responses in eliminating Salmonella infection. Full article
(This article belongs to the Special Issue Novel Vaccine Designs to Enhance the Engagement of Innate and Adaptive Immunity)
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14 pages, 1648 KB  
Article
Increase in Virus-Specific Mucosal Antibodies in the Upper Respiratory Tract Following Intramuscular Vaccination of Previously Exposed Horses Against Equine Herpesvirus Type-1/4
by Bettina Wagner, Christiane L. Schnabel and Alicia Rollins
Vaccines 2025, 13(3), 290; https://doi.org/10.3390/vaccines13030290 - 10 Mar 2025
Cited by 5 | Viewed by 1489
Abstract
Background/Objectives: Equine herpesvirus type-1 (EHV-1) enters through the upper respiratory tract (URT) and causes respiratory disease, abortions, and myeloencephalopathy in equids. Pre-existing immunity at the viral entry site, especially mucosal IgG4/7 antibodies, has recently been shown to correlate with protection from disease and [...] Read more.
Background/Objectives: Equine herpesvirus type-1 (EHV-1) enters through the upper respiratory tract (URT) and causes respiratory disease, abortions, and myeloencephalopathy in equids. Pre-existing immunity at the viral entry site, especially mucosal IgG4/7 antibodies, has recently been shown to correlate with protection from disease and incomplete viral replication at the URT. Here, we tested whether intramuscular (i.m.) vaccination with a commercial inactivated EHV-1/4 vaccine can induce mucosal antibodies (mucAbs) at the URT. Methods: Adult horses with complete EHV-1 vaccination and/or exposure histories were vaccinated i.m. six times within eight months. Before and after each vaccination, blood and nasal swab samples were obtained. Serum and mucAbs were measured in fluorescent bead-based EHV-1 assays. Results: All horses still had existing EHV-1 specific serum and mucAbs prior to vaccination, which were mainly composed of IgG4/7 antibody isotypes. Serum IgG4/7 significantly increased after the first vaccination and stayed high until the end of the study. An additional short-lasting serum IgG1 response was only induced by the first vaccine application. At the URT, mucAbs increased after five out of six i.m. vaccine injections. Like the systemic antibody response, mucAbs were dominated by IgG4/7 and a small IgG1 increase after the first vaccination. Conclusions: Our data emphasize that robust EHV-1 specific mucAb levels are obtained after i.m. vaccination with the inactivated EHV-1/4 vaccine used here. The findings have important implications for evaluating EHV-1/4 vaccines for their ability to induce and maintain protective mucosal IgG4/7 antibodies. Full article
(This article belongs to the Special Issue Veterinary Vaccines and Host Immune Responses)
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19 pages, 2598 KB  
Article
Prime-Boost Vaccination Based on Nanospheres and MVA Encoding the Nucleoprotein of Crimean-Congo Hemorrhagic Fever Virus Elicits Broad Immune Responses
by Eva Calvo-Pinilla, Sandra Moreno, Natalia Barreiro-Piñeiro, Juana M. Sánchez-Puig, Rafael Blasco, José Martínez-Costas, Alejandro Brun and Gema Lorenzo
Vaccines 2025, 13(3), 291; https://doi.org/10.3390/vaccines13030291 - 10 Mar 2025
Cited by 2 | Viewed by 2435
Abstract
Background/Objectives: Crimean–Congo hemorrhagic fever virus (CCHFV) is an emerging, widely distributed zoonotic tick-borne pathogen. The virus causes severe disease in humans, and numerous wild and domestic animals act as reservoirs of it. Unfortunately, there are no effective therapies or safe vaccines commercialized [...] Read more.
Background/Objectives: Crimean–Congo hemorrhagic fever virus (CCHFV) is an emerging, widely distributed zoonotic tick-borne pathogen. The virus causes severe disease in humans, and numerous wild and domestic animals act as reservoirs of it. Unfortunately, there are no effective therapies or safe vaccines commercialized nowadays for this particular virus. As CCHF (Crimean–Congo hemorrhagic fever) is a serious threat to public health, there is an urgent need to investigate the development of safe and effective vaccination strategies further. Methods: In this work, we have employed two immunization platforms based on protein nanoparticles and a modified vaccinia Ankara (MVA) viral vector using the nucleoprotein (NP) as the target antigen. The humoral and cellular immune responses were characterized by ELISA, ICS, and cytokine measurement. Results: This work shows that a single dose of the vaccine candidates was not as immunogenic as the heterologous vaccination using nanoparticles and MVA. A prime with NP nanoparticles (NS-NP) and a boost with MVA-expressing NP were capable of triggering significant levels of humoral and cellular immune responses against CCHFV in mice. Conclusions: Our study shows that the NS-NP/MVA-NP vaccination strategy effectively elicits a robust humoral and cellular immune response in a mouse model, emphasizing its potential as a protective approach against CCHFV lineages. Full article
(This article belongs to the Special Issue Veterinary Vaccines and Host Immune Responses)
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19 pages, 2176 KB  
Article
Evaluating the Immunogenicity of an Intranasal Microparticle Combination Vaccine for COVID-19 and Influenza
by Sharon Vijayanand, Smital Patil, Priyal Bagwe, Revanth Singh, Emmanuel Adediran and Martin J. D’Souza
Vaccines 2025, 13(3), 282; https://doi.org/10.3390/vaccines13030282 - 7 Mar 2025
Cited by 2 | Viewed by 2721
Abstract
Background: Infectious respiratory pathogens like SARS-CoV-2 and influenza frequently mutate, leading to the emergence of variants. This necessitates continuous updates to FDA-approved vaccines with booster shots targeting the circulating variants. Vaccine hesitancy and needle injections create inconvenience and contribute to reduced global vaccination [...] Read more.
Background: Infectious respiratory pathogens like SARS-CoV-2 and influenza frequently mutate, leading to the emergence of variants. This necessitates continuous updates to FDA-approved vaccines with booster shots targeting the circulating variants. Vaccine hesitancy and needle injections create inconvenience and contribute to reduced global vaccination rates. To address the burden of frequent painful injections, this manuscript explores the potential of non-invasive intranasal (IN) vaccine administration as an effective alternative to intramuscular (IM) shots. Further, as a proof-of-concept, an inactivated combination vaccine for COVID-19 and influenza was tested to eliminate the need for separate vaccinations. Methods: The methods involved encapsulating antigens and adjuvants in poly(lactic-co-glycolic acid) (PLGA) polymer matrices, achieving over 85% entrapment. The vaccine was evaluated in vitro for cytotoxicity and immunogenicity before being administered to 6–8-week-old Swiss Webster mice at weeks 0, 3, and 6. The mice were then assessed for antibody levels and cellular responses. Results: The intranasal microparticle (IN-MP) vaccine induced an innate immune response, autophagy, and were non-cytotoxic in vitro. In vivo, the vaccine led to high levels of virus-specific serum IgM, IgG, and IgA binding antibodies, as well as elevated IgG and IgA levels in the lung wash samples. The antibodies generated demonstrated neutralizing activity against the SARS-CoV-2 pseudovirus. Furthermore, the IN-MP vaccine prompted increased antigen-specific CD4+ and CD8+ T-cell responses in the vaccinated mice. Conclusions: The IN-MP combination vaccine produced immune responses comparable to or higher than the IM route, indicating its potential as an alternative to IM injections. Full article
(This article belongs to the Special Issue Innovating Vaccine Research in Mucosal Vaccines)
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20 pages, 3294 KB  
Systematic Review
Evaluating the Immunogenicity, Efficacy, and Effectiveness of Recombinant Zoster Vaccine for Global Public Health Policy
by Lucy R. Williams, Joachim Hombach and Melanie Marti
Vaccines 2025, 13(3), 250; https://doi.org/10.3390/vaccines13030250 - 27 Feb 2025
Cited by 5 | Viewed by 5966
Abstract
Background: Herpes zoster (HZ) is a painful neurocutaneous disease caused by the varicella-zoster virus. The recombinant zoster vaccine (RZV) is becoming increasingly incorporated into national vaccination schedules. We aimed to evaluate RZV from a global public health policy perspective. Methods: We [...] Read more.
Background: Herpes zoster (HZ) is a painful neurocutaneous disease caused by the varicella-zoster virus. The recombinant zoster vaccine (RZV) is becoming increasingly incorporated into national vaccination schedules. We aimed to evaluate RZV from a global public health policy perspective. Methods: We performed a rapid review of studies evaluating the immunogenicity, efficacy, and effectiveness of RZV for protection against HZ and associated complications. We searched PubMed for English-language studies published between 7 August 2012 and 30 September 2023. Included studies reported vaccine efficacy or effectiveness against HZ and HZ-associated complications. Immunogenicity studies were included if they contributed to the understanding of RZV protection over time and/or co-administration with other vaccines. HZ outcomes were stratified by socio-demographic and clinical variables. Results: From 405 identified publications, 33 were eligible for the study. Most studies were conducted in the US (N = 12), across North America (N = 10), and Europe (N = 5), or across multiple locations across North America, Latin America, and Asia–Australia (N = 6). Vaccine efficacy against HZ in immunocompetent populations ranged between 90% and 97%, while effectiveness ranged between 71% and 86%. Protection stayed above 70% for at least 10 years, with no significant differences by age or ethnicity. Conclusions: RZV is effective in reducing the risk of HZ and its associated complications. Protection is long-lasting and the vaccine is suitable for older and immunocompromised populations. However, the decision to incorporate the vaccine into national policies depends on additional factors (e.g., cost-effectiveness), which may be difficult to characterize without an understanding of the global disease burden. Full article
(This article belongs to the Special Issue 50 Years of Immunization—Steps Forward)
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14 pages, 3979 KB  
Article
Pre-Existing Anti-Vector Immunity to Adenovirus-Inspired VLP Vaccines Shows an Adjuvant-Dependent Antagonism
by Salomé Gallet, Dalil Hannani, Sebastian Dergan-Dylon, Emilie Vassal-Stermann, Isabelle Bally, Christopher Chevillard, Daphna Fenel, Olivier Epaulard, Pascal Poignard and Pascal Fender
Vaccines 2025, 13(3), 238; https://doi.org/10.3390/vaccines13030238 - 25 Feb 2025
Viewed by 2730
Abstract
Background/Objectives: The use of virus-like particles (VLPs) in vaccinology has expanded significantly in recent years. VLPs have the advantage of being non-infectious while effectively stimulating B cell responses through the repetitive presentation of epitope motifs on their surface. Since VLPs are often derived [...] Read more.
Background/Objectives: The use of virus-like particles (VLPs) in vaccinology has expanded significantly in recent years. VLPs have the advantage of being non-infectious while effectively stimulating B cell responses through the repetitive presentation of epitope motifs on their surface. Since VLPs are often derived from human-infecting viruses, preexisting immunity may influence the immune response they elicit, warranting further investigation. Methods: We have developed a 60-mer VLP derived from human adenovirus type 3, a common pathogen. We investigated the impact of pre-existing adenovirus immunity on the immunization outcome against the linear S14P5 epitope of SARS-CoV-2, which was engineered into the particle (Ad-VLP-S14P5). To this end, antibody responses to S14P5 were evaluated following immunization with Ad-VLP-S14P5 in either naive or vector-primed mice. Results: Mice with pre-existing anti-vector immunity exhibited significantly greater anti-S14P5 antibody responses compared to vector-naive animals, demonstrating a beneficial impact of prior anti-adenovirus responses. However, the addition of an oil-in-water adjuvant for the immunizations abolished this positive impact, even leading to a deleterious effect of the pre-existing anti-vector immunity. Conclusions: The data suggest that the immune status against immunizing VLPs must be taken into consideration when designing immunization protocols. Importantly, the effects of prior immunity may vary depending on the nature of the protocol, including factors such as adjuvant use. Full article
(This article belongs to the Special Issue Development of Vaccines Based on Virus-Like Particles: The 3rd Edition)
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31 pages, 1245 KB  
Review
Advances and Challenges in Aeromonas hydrophila Vaccine Development: Immunological Insights and Future Perspectives
by Kavi R. Miryala and Banikalyan Swain
Vaccines 2025, 13(2), 202; https://doi.org/10.3390/vaccines13020202 - 18 Feb 2025
Cited by 26 | Viewed by 6002
Abstract
Aeromonas hydrophila presents a significant threat to global aquaculture due to its ability to infect freshwater and marine fish species, leading to substantial economic losses. Effective mitigation methods are essential to address these challenges. Vaccination has emerged as a promising strategy to reduce [...] Read more.
Aeromonas hydrophila presents a significant threat to global aquaculture due to its ability to infect freshwater and marine fish species, leading to substantial economic losses. Effective mitigation methods are essential to address these challenges. Vaccination has emerged as a promising strategy to reduce A. hydrophila infections; however, it faces several obstacles, including variability in immune responses, pathogen diversity, and environmental factors affecting vaccine efficacy. To enhance vaccine performance, researchers focus on adjuvants to boost immune responses and develop multivalent vaccines targeting multiple A. hydrophila strains. Tailoring vaccines to specific environmental conditions and optimizing vaccination schedules can further address the challenges posed by pathogen diversity and variable immune responses. This review provides an in-depth analysis of the immunological hurdles associated with A. hydrophila vaccine development. Current vaccine types—live attenuated, inactivated, subunit, recombinant, and DNA—exhibit diverse mechanisms for stimulating innate and adaptive immunity, with varying levels of success. Key focus areas include the potential of advanced adjuvants and nanoparticle delivery systems to overcome existing barriers. The review also highlights the importance of understanding host–pathogen interactions in guiding the development of more targeted and effective immune responses in fish. Complementary approaches, such as immunostimulants, probiotics, and plant-based extracts, are explored as adjuncts to vaccination in aquaculture health management. Despite notable progress, challenges remain in translating laboratory innovations into scalable, cost-effective solutions for aquaculture. Future directions emphasize the integration of advanced genomic and proteomic tools to identify novel antigen candidates and the need for industry-wide collaborations to standardize vaccine production and delivery. Addressing these challenges can unlock the potential of innovative vaccine technologies to safeguard fish health and promote sustainable aquaculture practices globally. Full article
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29 pages, 2354 KB  
Review
Molecular Farming for Immunization: Current Advances and Future Prospects in Plant-Produced Vaccines
by Dang-Khoa Vo and Kieu The Loan Trinh
Vaccines 2025, 13(2), 191; https://doi.org/10.3390/vaccines13020191 - 15 Feb 2025
Cited by 19 | Viewed by 13567
Abstract
Using plants as bioreactors, molecular farming has emerged as a versatile and sustainable platform for producing recombinant vaccines, therapeutic proteins, industrial enzymes, and nutraceuticals. This innovative approach leverages the unique advantages of plants, including scalability, cost-effectiveness, and reduced risk of contamination with human [...] Read more.
Using plants as bioreactors, molecular farming has emerged as a versatile and sustainable platform for producing recombinant vaccines, therapeutic proteins, industrial enzymes, and nutraceuticals. This innovative approach leverages the unique advantages of plants, including scalability, cost-effectiveness, and reduced risk of contamination with human pathogens. Recent advancements in gene editing, transient expression systems, and nanoparticle-based delivery technologies have significantly enhanced the efficiency and versatility of plant-based systems. Particularly in vaccine development, molecular farming has demonstrated its potential with notable successes such as Medicago’s Covifenz for COVID-19, illustrating the capacity of plant-based platforms to address global health emergencies rapidly. Furthermore, edible vaccines have opened new avenues in the delivery of vaccines, mainly in settings with low resources where the cold chain used for conventional logistics is a challenge. However, optimization of protein yield and stability, the complexity of purification processes, and regulatory hurdles are some of the challenges that still remain. This review discusses the current status of vaccine development using plant-based expression systems, operational mechanisms for plant expression platforms, major applications in the prevention of infectious diseases, and new developments, such as nanoparticle-mediated delivery and cancer vaccines. The discussion will also touch on ethical considerations, the regulatory framework, and future trends with respect to the transformative capacity of plant-derived vaccines in ensuring greater global accessibility and cost-effectiveness of the vaccination. This field holds great promise for the infectious disease area and, indeed, for applications in personalized medicine and biopharmaceuticals in the near future. Full article
(This article belongs to the Special Issue Production of Plant-Based Vaccines and Therapeutics)
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28 pages, 798 KB  
Review
Progress and Challenges in HIV-1 Vaccine Research: A Comprehensive Overview
by Alex C. Boomgarden and Chitra Upadhyay
Vaccines 2025, 13(2), 148; https://doi.org/10.3390/vaccines13020148 - 31 Jan 2025
Cited by 18 | Viewed by 24985
Abstract
The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements in our understanding of HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, and its ability [...] Read more.
The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements in our understanding of HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, and its ability to establish latent reservoirs. Recent innovative approaches, including mosaic vaccines and mRNA technology to induce broadly neutralizing antibodies, have shown promise. However, the efficacy of these vaccines has been modest, with the best results achieving approximately 30% effectiveness. Ongoing research emphasizes the necessity of a multifaceted strategy to overcome these obstacles and achieve a breakthrough in HIV-1 vaccine development. This review summarizes current approaches utilized to further understand HIV-1 biology and to create a global vaccine. We discuss the impact of these approaches on vaccine development for other diseases, including COVID-19, influenza, and Zika virus. Additionally, we highlight the specific limitations faced with each approach and present the methods researchers employ to overcome these challenges. These innovative techniques, which have demonstrated preclinical and clinical success, have advanced the field closer to the ultimate goal of developing a global HIV-1 vaccine. Leveraging these advancements will enable significant strides in combating HIV-1 and other infectious diseases, ultimately improving global health outcomes. Full article
(This article belongs to the Special Issue Advances in HIV Vaccine Development)
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19 pages, 8275 KB  
Article
Adenoviral Vector-Based Vaccine Expressing Hemagglutinin Stem Region with Autophagy-Inducing Peptide Confers Cross-Protection Against Group 1 and 2 Influenza A Viruses
by Wen-Chien Wang, Ekramy E. Sayedahmed, Marwa Alhashimi, Ahmed Elkashif, Vivek Gairola, Muralimanohara S. T. Murala, Suryaprakash Sambhara and Suresh K. Mittal
Vaccines 2025, 13(1), 95; https://doi.org/10.3390/vaccines13010095 - 20 Jan 2025
Cited by 5 | Viewed by 3297
Abstract
Background/Objectives: An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. Methods: In this study, bovine and human adenoviral vector-based vaccine platforms were [...] Read more.
Background/Objectives: An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. Methods: In this study, bovine and human adenoviral vector-based vaccine platforms were utilized to express various combinations of antigens. These included the H5N1 hemagglutinin (HA) stem region or HA2, the extracellular domain of matrix protein 2 of influenza A virus, HA signal peptide (SP), trimerization domain, excretory peptide, and the autophagy-inducing peptide C5 (AIP-C5). The goal was to identify the optimal combination for enhanced immune responses and cross-protection. Mice were immunized using a prime-boost strategy with heterologous adenoviral (Ad) vectors. Results: The heterologous Ad vectors induced robust HA stem-specific humoral and cellular immune responses in the immunized mice. Among the tested combinations, Ad vectors expressing SP + HA stem + AIP-C5 conferred significant protection against group 1 (H1N1 and H5N1) and group 2 (H3N2) influenza A viruses. This protection was demonstrated by lower lung viral titers and reduced morbidity and mortality. Conclusions: The findings support further investigation of heterologous Ad vaccine platforms expressing SP + HA stem + AIP-C5. This combination shows promise as a potential universal influenza vaccine, providing broader protection against influenza A viruses. Full article
(This article belongs to the Special Issue Advances in Vaccines Against Infectious Diseases)
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14 pages, 1446 KB  
Article
Persistence of the Immune Response to an Intramuscular Bivalent (GI.1/GII.4) Norovirus Vaccine in Adults
by Geert Leroux-Roels, Robert L. Atmar, Jakob P. Cramer, Ian Escudero and Astrid Borkowski
Vaccines 2025, 13(1), 82; https://doi.org/10.3390/vaccines13010082 - 17 Jan 2025
Cited by 6 | Viewed by 3539
Abstract
Background: Major global economic and health burdens due to norovirus gastroenteritis could be addressed by an effective vaccine. Methods: In this study, 428 adult recipients of various compositions of the norovirus vaccine candidate, HIL-214, were followed for 5 years, to assess immune responses [...] Read more.
Background: Major global economic and health burdens due to norovirus gastroenteritis could be addressed by an effective vaccine. Methods: In this study, 428 adult recipients of various compositions of the norovirus vaccine candidate, HIL-214, were followed for 5 years, to assess immune responses to its virus-like particle antigens, GI.1 and GII.4c. Serum antibodies and peripheral-blood antibody-secreting cells (ASCs) were measured. This report focuses on the single-dose 15/50 (µg GI.1/GII.4c) composition, which had been selected for further clinical development. Results: For single-dose 15/50 recipients (N = 105), GI.1-specific and GII.4c-specific histoblood-group antigen-blocking (HBGA) antibodies appeared to have persisted to 5 years, waning from a peak at 4 to 8 weeks, and plateauing above baseline after 3 years. From 3 to 5 years, GI.1-specific GMTs ranged between 53 (95%CI, 40–71) and 60 (95%CI, 46–77; N = 69–97) and were approximately 2-fold above the baseline GMT (24 (95%CI, 20–28); N = 105). GII.4c-specific GMTs ranged between 103 (95%CI, 77–138) and 114 (95%CI, 86–152; N = 70–97) and were above baseline, but by less than 2-fold (70 (95%CI, 53–92); N = 105). Similar kinetics were observed for pan-Ig titers and ASCs in a subset. Similar kinetics were also observed for HBGA and pan-Ig titers in recipients of other 15/50 dosages. Conclusions: Immune responses to HIL-214 in adults appear to persist for five years. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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15 pages, 272 KB  
Review
Pertussis Vaccination for Adults: An Updated Guide for Clinicians
by Kay Choong See
Vaccines 2025, 13(1), 60; https://doi.org/10.3390/vaccines13010060 - 11 Jan 2025
Cited by 10 | Viewed by 10856
Abstract
Pertussis, or whooping cough, is a highly contagious respiratory infection caused by the Gram-negative bacterium Bordetella pertussis. Although traditionally associated with children, pertussis is increasingly prevalent among adults, particularly those with comorbidities or weakened immune systems, where it can lead to severe [...] Read more.
Pertussis, or whooping cough, is a highly contagious respiratory infection caused by the Gram-negative bacterium Bordetella pertussis. Although traditionally associated with children, pertussis is increasingly prevalent among adults, particularly those with comorbidities or weakened immune systems, where it can lead to severe complications. Diagnosing pertussis in adults can be challenging due to its nonspecific symptoms, underreporting, and the limited sensitivity of available diagnostic tests. While treatment with macrolides is generally effective, it may not significantly alter the clinical course of the disease, and growing concerns about macrolide resistance are emerging. Vaccination remains the cornerstone of prevention, offering proven immunogenicity, efficacy, and safety. However, vaccination uptake remains low, partly due to limited patient awareness and insufficient prioritization by healthcare professionals. This review aims to provide clinicians with critical insights into pertussis epidemiology, vaccination strategies, and the latest guideline recommendations, empowering them to engage in meaningful discussions with adult patients and advocate for increased vaccination to combat this often-overlooked infection. Full article
(This article belongs to the Special Issue Vaccination Uptake and Public Health)
18 pages, 2085 KB  
Review
Lipoprotein Signal Peptide as Adjuvants: Leveraging Lipobox-Driven TLR2 Activation in Modern Vaccine Design
by Muhammad Umar, Haroon Afzal, Asad Murtaza and Li-Ting Cheng
Vaccines 2025, 13(1), 36; https://doi.org/10.3390/vaccines13010036 - 2 Jan 2025
Cited by 5 | Viewed by 4722
Abstract
Toll-like receptor 2 (TLR2) signaling is a pivotal component of immune system activation, and it is closely linked to the lipidation of bacterial proteins. This lipidation is guided by bacterial signal peptides (SPs), which ensure the precise targeting and membrane anchoring of these [...] Read more.
Toll-like receptor 2 (TLR2) signaling is a pivotal component of immune system activation, and it is closely linked to the lipidation of bacterial proteins. This lipidation is guided by bacterial signal peptides (SPs), which ensure the precise targeting and membrane anchoring of these proteins. The lipidation process is essential for TLR2 recognition and the activation of robust immune responses, positioning lipidated bacterial proteins as potent immunomodulators and adjuvants for vaccines against bacterial-, viral-, and cancer-related antigens. The structural diversity and cleavage pathways of bacterial SPs are critical in determining lipidation efficiency and protein localization, influencing their immunogenic potential. Recent advances in bioinformatics have significantly improved the prediction of SP structures and cleavage sites, facilitating the rational design of recombinant lipoproteins optimized for immune activation. Moreover, the use of SP-containing lipobox motifs, as adjuvants to lipidate heterologous proteins, has expanded the potential of vaccines targeting a broad range of pathogens. However, challenges persist in expressing lipidated proteins, particularly within heterologous systems. These challenges can be addressed by optimizing expression systems, such as engineering E. coli strains for enhanced lipidation. Thus, lipoprotein signal peptides (SPs) demonstrate remarkable versatility as adjuvants in vaccine development, diagnostics, and immune therapeutics, highlighting their essential role in advancing immune-based strategies to combat diverse pathogens. Full article
(This article belongs to the Special Issue State-of-the-Art Vaccine Design)
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15 pages, 5522 KB  
Article
Cell Wall Protein 2 as a Vaccine Candidate Protects Mice Against Clostridioides difficile Infection
by Shaohui Wang, Joshua Heuler, Jessica Bullock, Junling Qin, Soumyadeep Chakraborty, Agbendeh Lubem Nathaniel, Shifeng Wang and Xingmin Sun
Vaccines 2025, 13(1), 21; https://doi.org/10.3390/vaccines13010021 - 30 Dec 2024
Cited by 8 | Viewed by 2323
Abstract
Background/Objectives: Clostridioides difficile is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for C. difficile infection (CDI) involve a limited selection of antibiotics that are not fully effective, leading to high [...] Read more.
Background/Objectives: Clostridioides difficile is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for C. difficile infection (CDI) involve a limited selection of antibiotics that are not fully effective, leading to high recurrence rates. Vaccination presents a promising strategy for preventing both CDI and its recurrence. Cell wall protein 2 (Cwp2), a highly immunogenic and abundant surface-exposed C. difficile cell wall protein, plays an important role in the bacterium’s adherence in vitro. In this study, we aimed to analyze the homology and immunogenicity of Cwp2 and its protection efficacy as a vaccine candidate against CDI in mice. Methods: we conducted in silico analyses to assess the homology and immunogenicity of Cwp2, and we evaluated its potential as a vaccine candidate against CDI using a mouse model of immunization and infection. Results: Our in silico analyses predicted the immunogenic region (functional domain) of Cwp2 and revealed its high homology among various toxinotypes and ribotypes (R.T.s) or sequence types (S.T.s). Immunizations of mice with the Cwp2 functional domain (Cwp2_A) induced potent IgG/A antibody responses against Cwp2_A, protected mice from CDI, and reduced C. difficile spore and toxin levels in feces post-infection. Additionally, anti-Cwp2_A sera inhibited the binding of C. difficile vegetative cells to HCT8 cells. Conclusions: Our report demonstrates for the first time the potential of Cwp2_A as an effective vaccine candidate against CDI in mice. Full article
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16 pages, 615 KB  
Review
Durability of Adaptive Immunity in Immunocompetent and Immunocompromised Patients Across Different Respiratory Viruses: RSV, Influenza, and SARS-CoV-2
by Achilleas Livieratos, Lars Erik Schiro, Charalambos Gogos and Karolina Akinosoglou
Vaccines 2024, 12(12), 1444; https://doi.org/10.3390/vaccines12121444 - 22 Dec 2024
Cited by 5 | Viewed by 5483
Abstract
Background/Objectives. Research on respiratory virus immunity duration post-vaccination reveals variable outcomes. This study performed a literature review to assess the efficacy and longevity of immune protection post-vaccination against SARS-CoV-2, influenza, and respiratory syncytial virus (RSV), with a focus on immunocompromised populations. Specific objectives [...] Read more.
Background/Objectives. Research on respiratory virus immunity duration post-vaccination reveals variable outcomes. This study performed a literature review to assess the efficacy and longevity of immune protection post-vaccination against SARS-CoV-2, influenza, and respiratory syncytial virus (RSV), with a focus on immunocompromised populations. Specific objectives included examining humoral and cellular immune responses and exploring the impact of booster doses and hybrid immunity on extending protection. Methods. A literature review was conducted focusing on studies published from January 2014 to November 2024. The search targeted adaptive immunity post-vaccination, natural immunity, and hybrid immunity for SARS-CoV-2, influenza, and RSV. Selection criteria emphasized human populations, adaptive immunity outcomes, and immunocompromised individuals. The PICO framework guided the analysis, culminating in a detailed review of 30 studies. Results. SARS-CoV-2 vaccines exhibited robust initial antibody responses, which waned significantly within six months, necessitating frequent boosters. Influenza and RSV vaccines similarly showed declines in immunity, though some influenza vaccines demonstrated moderate durability. Hybrid immunity, arising from combined natural infection and vaccination, provided more resilient and lasting protection than vaccination alone, especially against emerging variants. Immunocompromised individuals consistently exhibited reduced durability in adaptive immune responses across all studied viruses. Challenges include rapid viral mutations, limiting the broad protection of current vaccines. Conclusions. Immune durability varies significantly across virus types and patient populations. Frequent boosters and hybrid immunity are critical to optimizing protection, particularly for vulnerable groups. The findings underscore the need for adaptable vaccination strategies and advancements in vaccine design to counter rapidly mutating respiratory pathogens effectively. Full article
(This article belongs to the Special Issue Analysis of Vaccine-Induced Adaptive Immune Responses)
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8 pages, 447 KB  
Article
Immunoprophylaxis with MV140 Is Effective in the Reduction of Urinary Tract Infections—A Prospective Real-Life Study
by Filipe Abadesso Lopes, Miguel Miranda, André Ye, Joana Rodrigues, Paulo Pé-Leve, José Palma Reis and Ricardo Pereira e Silva
Vaccines 2024, 12(12), 1426; https://doi.org/10.3390/vaccines12121426 - 18 Dec 2024
Cited by 5 | Viewed by 5820
Abstract
Background/Objectives: Urinary tract infections (UTI) represent a highly frequent and debilitating disease. Immunoactive prophylaxis, such as the polyvalent bacterial whole-cell-based sublingual vaccine MV140, have been developed to avoid antibiotic use. However, the effectiveness of this tool in the Portuguese population is still unknown. [...] Read more.
Background/Objectives: Urinary tract infections (UTI) represent a highly frequent and debilitating disease. Immunoactive prophylaxis, such as the polyvalent bacterial whole-cell-based sublingual vaccine MV140, have been developed to avoid antibiotic use. However, the effectiveness of this tool in the Portuguese population is still unknown. This study aims at assessing the effectiveness of treatment with MV140 in a cohort of Portuguese patients presenting with recurrent UTIs. Methods: Prospective observational real-life study of 125 patients with complicated and uncomplicated recurrent UTIs treated with MV140. The primary outcome was a reduction in frequency and severity of UTIs after a follow-up of 12 months. Overall satisfaction, adverse events, and assessment of the effectiveness of MV140 in subgroups of patients with specific risk factors for UTIs were secondary outcomes. Results: In the 12 months after treatment outset, 38% of patients were UTI-free, 34% reported 1 or 2 UTI episodes, and the remaining 28% presented 3 or more UTIs, corresponding to a mean reduction of 3.20 (2.87–3.53, 95% C.I.; p < 0.001) UTI episodes per year per patient. The effectiveness of MV140 was the same regardless of sex, BMI, regular sexual activity, hypertension, diabetes mellitus, depression, paraplegia, performance of intermittent self-catheterization, indwelling bladder catheter, or previous use of other UTI-preventing vaccines. We observed a higher effectiveness in post-menopausal women compared to pre-menopausal (74.7% vs. 59.4%, respectively, p = 0.029). A total of 73% of patients reported a reduction in symptom severity or days of disease, and the mean global satisfaction was 7.52/10. Conclusions: MV140 demonstrated to be effective in the reduction rate of recurrent UTIs in a cohort of adult Portuguese patients. Full article
(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)
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20 pages, 9291 KB  
Article
Development Using Bioluminescence Imaging of a Recombinant Anguillid Herpesvirus 1 Vaccine Candidate Associated with Normal Replication In Vitro but Abortive Infection In Vivo
by Haiyan Zhang, Arun Sridhar, Natacha Delrez, Bo He, Sophie Fourny, Yuan Gao, Owen Donohoe and Alain F. C. Vanderplasschen
Vaccines 2024, 12(12), 1423; https://doi.org/10.3390/vaccines12121423 - 17 Dec 2024
Cited by 3 | Viewed by 2328
Abstract
Background/Objectives: Anguillid herpesvirus 1 (AngHV-1) (recently renamed Cyvirus anguillidallo 1) is the etiologic agent of a lethal disease that affects several eel species. It is thought to be one of the main infectious agents causing a population decline in wild eels and economic [...] Read more.
Background/Objectives: Anguillid herpesvirus 1 (AngHV-1) (recently renamed Cyvirus anguillidallo 1) is the etiologic agent of a lethal disease that affects several eel species. It is thought to be one of the main infectious agents causing a population decline in wild eels and economic loss within the eel aquaculture sector. To date, no vaccines are available against AngHV-1. Recently, we developed a safe and efficacious live attenuated recombinant vaccine against Cyprinid herpesvirus 3 (CyHV-3). This CyHV-3 recombinant vaccine encodes a deletion of ORF57. Orthologues of CyHV-3 ORF57 exist in Cyprinid herpesvirus 2 (CyHV-2, ORF57) and AngHV-1 (ORF35). Methods: In the present study, using recombinant strains and bioluminescent in vivo imaging, we investigated the effect of AngHV-1 ORF35 deletion on virus replication in vitro, virulence in vivo, and the potential of an AngHV-1 ORF35-deleted recombinant as a vaccine candidate for the mass vaccination of eels by immersion. With this goal in mind, we produced ORF35-deleted recombinants using two parental strains: a UK strain and a recombinant derived from the former strain by insertion of a Luciferase–GFP reporter cassette into a non-coding intergenic region. Results: Analyses of ORF35-deleted recombinants led to the following observations: (i) AngHV-1 ORF35 is not essential for viral growth in cell culture, and its deletion does not affect the production of extracellular virions despite reducing the size of viral plaque. (ii) In contrast to what has been observed for CyHV-3 ORF57 and CyHV-2 ORF57, in vivo bioluminescent analyses revealed that AngHV-1 ORF35 is an essential virulence factor and that its deletion led to abortive infection in vivo. (iii) Inoculation of the AngHV-1 ORF35-deleted recombinant by immersion induced a protective immune response against a wild-type challenge. This protection was shown to be dose-dependent and to rely on the infectivity of AngHV-1 ORF35-deleted virions. Conclusions: This study suggests that the AngHV-1 ORF35 protein has singular properties compared to its orthologues encoded by CyHV-2 and CyHV-3. It also supports the potential of AngHV-1 ORF35-deleted recombinants for the mass vaccination of eels by immersion. Full article
(This article belongs to the Special Issue Animal Herpesviruses)
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15 pages, 1318 KB  
Review
The Strategic Advisory Group of Experts (SAGE) on Immunization—Past, Present and Future
by Melanie Marti, Hanna Nohynek, Philippe Duclos, Katherine L. O’Brien and Joachim Hombach
Vaccines 2024, 12(12), 1402; https://doi.org/10.3390/vaccines12121402 - 12 Dec 2024
Cited by 12 | Viewed by 10798
Abstract
Background/Objectives: In November 1999, WHO established the Strategic Advisory Group of Experts (SAGE) on Immunization as a multidisciplinary group of experts to provide high-level recommendations on vaccines and immunization. Methods: This review provides an overview of SAGE’s work in the past 25 years. [...] Read more.
Background/Objectives: In November 1999, WHO established the Strategic Advisory Group of Experts (SAGE) on Immunization as a multidisciplinary group of experts to provide high-level recommendations on vaccines and immunization. Methods: This review provides an overview of SAGE’s work in the past 25 years. It further outlines the processes and methods currently used by SAGE and highlights some of its major achievements. Results: SAGE’s global policies have driven action toward eradication, elimination and disease control and addressed the optimization of vaccination and immunization. In total, 27 major policy positions on vaccines/vaccine-preventable diseases have guided global public health. During times of epidemics and pandemics, interim recommendations issued by SAGE have responded iteratively in real-time to provide evidence-driven response policies. SAGE is an adaptive advisory group that has modified its procedures and working approaches to meet the evolving challenges in public health and stay up-to-date with evolving scientific and guideline development standards. Conclusions: Over the last quarter century, SAGE has significantly contributed to shaping the immunization landscape. It has achieved and maintained a high level of integrity and credibility. The advisory group continues to be an authority in global public health, and its recommendations have profound implications for the health of individuals and populations across the globe. Full article
(This article belongs to the Special Issue 50 Years of Immunization—Steps Forward)
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24 pages, 1824 KB  
Article
Safety, Immunogenicity, and Efficacy of a Recombinant Vesicular Stomatitis Virus Vectored Vaccine Against Severe Fever with Thrombocytopenia Syndrome Virus and Heartland Bandavirus
by Philip Hicks, Tomaz B. Manzoni, Jonna B. Westover, Raegan J. Petch, Brianne Roper, Brian B. Gowen and Paul Bates
Vaccines 2024, 12(12), 1403; https://doi.org/10.3390/vaccines12121403 - 12 Dec 2024
Cited by 10 | Viewed by 3595
Abstract
Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite [...] Read more.
Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation, and promiscuity in incorporating foreign glycoproteins into its virions. Methods: In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity, and efficacy in C57BL/6, Ifnar−/−, and AG129 mice. Results: We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of wild type (C57BL/6) and Ifnar−/− mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection in a lethal SFTSV challenge model. Additionally, passive transfer of sera from immunized Ifnar−/− mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects AG129 mice against challenge with the closely related Heartland bandavirus despite negligible neutralizing titers to the virus. Conclusions: Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate for SFTSV and Heartland bandavirus with a favorable safety profile. Full article
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34 pages, 3445 KB  
Review
Approaches to Enhance the Potency of Vaccines in Chickens
by Oenone Bodman-Harris, Christine S. Rollier and Munir Iqbal
Vaccines 2024, 12(12), 1337; https://doi.org/10.3390/vaccines12121337 - 27 Nov 2024
Cited by 11 | Viewed by 11636
Abstract
Outbreaks of avian pathogens such as Newcastle disease virus, avian influenza virus, and salmonella have a major impact on economies and food security worldwide. Some pathogens also pose a significant zoonotic potential, especially avian influenza viruses. Vaccination plays a key role in controlling [...] Read more.
Outbreaks of avian pathogens such as Newcastle disease virus, avian influenza virus, and salmonella have a major impact on economies and food security worldwide. Some pathogens also pose a significant zoonotic potential, especially avian influenza viruses. Vaccination plays a key role in controlling many poultry diseases, and there are many vaccines licenced in the United Kingdom for diseases of poultry caused by viruses, bacteria, and parasites. However, these vaccines often do not provide complete protection and can cause unwanted side effects. Several factors affect the potency of poultry vaccines, including the type of vaccination used, the mechanism of delivery, and the use of adjuvants. Advancements in technology have led to the study and development of novel vaccines and vaccine adjuvants for use in poultry. These induce stronger immune responses compared with current vaccine technology and have the potential to protect against multiple poultry diseases. This review aims to discuss the existing poultry vaccine technology; the effect of delivery mechanisms on vaccine efficacy; the use of current and novel adjuvants; the ability to target antigens to antigen-presenting cells; and the use of probiotics, multivalent vaccines, and nanotechnology to enhance the potency of poultry vaccines. Full article
(This article belongs to the Special Issue Vaccines Against Poultry Viruses)
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24 pages, 5421 KB  
Article
Rapid Development of Modified Vaccinia Virus Ankara (MVA)-Based Vaccine Candidates Against Marburg Virus Suitable for Clinical Use in Humans
by Alina Tscherne, Georgia Kalodimou, Alexandra Kupke, Cornelius Rohde, Astrid Freudenstein, Sylvia Jany, Satendra Kumar, Gerd Sutter, Verena Krähling, Stephan Becker and Asisa Volz
Vaccines 2024, 12(12), 1316; https://doi.org/10.3390/vaccines12121316 - 24 Nov 2024
Cited by 5 | Viewed by 4588
Abstract
Background/Objectives: Marburg virus (MARV) is the etiological agent of Marburg Virus Disease (MVD), a rare but severe hemorrhagic fever disease with high case fatality rates in humans. Smaller outbreaks have frequently been reported in countries in Africa over the last few years, and [...] Read more.
Background/Objectives: Marburg virus (MARV) is the etiological agent of Marburg Virus Disease (MVD), a rare but severe hemorrhagic fever disease with high case fatality rates in humans. Smaller outbreaks have frequently been reported in countries in Africa over the last few years, and confirmed human cases outside Africa are, so far, exclusively imported by returning travelers. Over the previous years, MARV has also spread to non-endemic African countries, demonstrating its potential to cause epidemics. Although MARV-specific vaccines are evaluated in preclinical and clinical research, none have been approved for human use. Modified Vaccinia virus Ankara (MVA), a well-established viral vector used to generate vaccines against emerging pathogens, can deliver multiple antigens and has a remarkable clinical safety and immunogenicity record, further supporting its evaluation as a vaccine against MARV. The rapid availability of safe and effective MVA-MARV vaccine candidates would expand the possibilities of multi-factored intervention strategies in endemic countries. Methods: We have used an optimized methodology to rapidly generate and characterize recombinant MVA candidate vaccines that meet the quality requirements to proceed to human clinical trials. As a proof-of-concept for the optimized methodology, we generated two recombinant MVAs that deliver either the MARV glycoprotein (MVA-MARV-GP) or the MARV nucleoprotein (MVA-MARV-NP). Results: Infections of human cell cultures with recombinant MVA-MARV-GP and MVA-MARV-NP confirmed the efficient synthesis of MARV-GP and MARV-NP proteins in mammalian cells, which are non-permissive for MVA replication. Prime-boost immunizations in C57BL/6J mice readily induced circulating serum antibodies binding to recombinant MARV-GP and MARV-NP proteins. Moreover, the MVA-MARV-candidate vaccines elicited MARV-specific T-cell responses in C57BL/6J mice. Conclusions: We confirmed the suitability of our two backbone viruses MVA-mCherry and MVA-GFP in a proof-of-concept study to rapidly generate candidate vaccines against MARV. However, further studies are warranted to characterize the protective efficacy of these recombinant MVA-MARV vaccines in other preclinical models and to evaluate them as vaccine candidates in humans. Full article
(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)
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14 pages, 10252 KB  
Review
Childhood Mandatory Vaccinations: Current Situation in European Countries and Changes Occurred from 2014 to 2024
by Sara Farina, Alessandra Maio, Maria Rosaria Gualano, Walter Ricciardi and Leonardo Villani
Vaccines 2024, 12(11), 1296; https://doi.org/10.3390/vaccines12111296 - 20 Nov 2024
Cited by 16 | Viewed by 14271
Abstract
Background/Objectives: Vaccination is one of the most effective public health interventions, preventing millions of deaths globally each year. However, vaccine hesitancy, driven by misinformation and reduced disease risk perception, has led to declining vaccination rates and the resurgence of vaccine-preventable diseases (VPDs) [...] Read more.
Background/Objectives: Vaccination is one of the most effective public health interventions, preventing millions of deaths globally each year. However, vaccine hesitancy, driven by misinformation and reduced disease risk perception, has led to declining vaccination rates and the resurgence of vaccine-preventable diseases (VPDs) in Europe. In response to this, countries have implemented various strategies, including mandatory and recommended vaccination programs. The objective of this study is to map the current European landscape of pediatric vaccination policies, and the variations that have occurred in the last decade. Methods: This rapid review was conducted on PubMed, Google, and the European Centre for Disease Prevention and Control website, to collect all vaccination schedules in EU/EEA countries in 2024 and all documents focusing on the introduction of mandatory vaccines during the last decade. Results: As of 2024, 13 countries had at least one mandatory pediatric vaccination, with France, Hungary, and Latvia requiring all but one vaccine. In contrast, 17 countries had no mandatory vaccinations, relying only on recommendations. Between 2014 and 2024, six countries (Croatia, France, Germany, Hungary, Italy, and Poland) introduced or extended mandatory vaccinations. Conclusions: European vaccination policies show significant variation. Effective programs depend on robust healthcare systems, public trust, and adaptable strategies to address vaccine hesitancy and the resurgence of VPDs. Full article
(This article belongs to the Special Issue Advance Public Health Through Vaccination)
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12 pages, 2248 KB  
Review
Immune Checkpoint Inhibitors and Vaccination: Assessing Safety, Efficacy, and Synergistic Potential
by Jacob New, Luke Shenton, Radia Ksayer, Justin Wang, Karam Zakharia, Laura J. Nicholson and Amitabh C. Pandey
Vaccines 2024, 12(11), 1270; https://doi.org/10.3390/vaccines12111270 - 11 Nov 2024
Cited by 8 | Viewed by 5519
Abstract
Although immune checkpoint inhibitors (ICIs) have become predominant therapies for cancer, the safety and efficacy of combining ICIs with vaccinations remain areas of needed investigation. As ICIs gain broader clinical application, the relevance of current vaccination guidelines for cancer patients—largely developed in the [...] Read more.
Although immune checkpoint inhibitors (ICIs) have become predominant therapies for cancer, the safety and efficacy of combining ICIs with vaccinations remain areas of needed investigation. As ICIs gain broader clinical application, the relevance of current vaccination guidelines for cancer patients—largely developed in the context of cytotoxic therapies—becomes increasingly uncertain. Although data support the safety of combining inactivated influenza and mRNA SARS-CoV-2 vaccines with ICI therapy, comprehensive data on other infectious disease vaccines remain scarce. Notably, the combination of ICIs with infectious disease vaccines does not appear to exacerbate immune-related adverse events, despite the heightened cytokine activity observed. However, the efficacy of vaccines administered alongside ICIs in preventing infectious diseases remains poorly supported by robust evidence. Preliminary findings suggest a potential survival benefit in cancer patients receiving ICI therapy alongside influenza or SARS-CoV-2 vaccination, though the quality of evidence is currently low. Moreover, the synergistic potential of combining therapeutic cancer vaccines, particularly mRNA-based vaccines, with ICIs indicates promise but with a paucity of phase III data to confirm efficacy. This review critically examines the safety and efficacy of combining ICIs with both infectious disease vaccines and therapeutic cancer vaccines. While vaccination appears safe in patients undergoing ICI therapy, the impact on infectious disease prevention and cancer treatment outcomes warrants further rigorous investigation. Full article
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15 pages, 706 KB  
Article
Lessons from Recent Measles Post-Campaign Coverage Surveys Worldwide
by M. Carolina Danovaro-Holliday, Mitsuki Koh, Claudia Steulet, Dale A. Rhoda and Mary Kay Trimner
Vaccines 2024, 12(11), 1257; https://doi.org/10.3390/vaccines12111257 - 6 Nov 2024
Cited by 3 | Viewed by 3368
Abstract
Background: Measles elimination strategies include supplementary immunization activities (SIAs) to rapidly fill immunity gaps. Post-campaign coverage surveys (PCCSs) are recommended to assess SIA coverage. We characterized selected PCCSs performed following recent SIAs, highlighting specific challenges and strengths, and provide recommendations for improvement. Methods: [...] Read more.
Background: Measles elimination strategies include supplementary immunization activities (SIAs) to rapidly fill immunity gaps. Post-campaign coverage surveys (PCCSs) are recommended to assess SIA coverage. We characterized selected PCCSs performed following recent SIAs, highlighting specific challenges and strengths, and provide recommendations for improvement. Methods: We extracted national SIA data from the global measles/MR SIA database for the period of 2020–2023 and reviewed PCCS reports available at the World Health Organization headquarters. We extracted selected information on PCCS implementation, including information about the implementer, sampling, and main results. Results: Only 15 of 66 countries (23%) with a national-level SIA performed since 2020 had a PCCS report available. We reviewed those reports, plus six more, following three 2019 SIAs with a delayed PCCS and two PCCSs following large subnational SIAs (Kenya 2021 and Yemen 2023). All 24 PCCS reports available were from Gavi-eligible countries, with 15 from South Saharan Africa (Cameroon, the Democratic Republic of the Congo, and Ethiopia had two PCCSs). Eleven (45.8%) PCCSs were conducted within three months of the end of the SIA. All included sampling information and most had percentage of participation. Description of the interviewers’ profiles varied but was limited. PCCS coverage was lower than administrative data in all but two instances. All PCCSs collected data on previous measles vaccination status that would allow exploring indicators on the SIA reaching previously measles zero-dose children. Of the 12 PCCSs reporting coverage among previously measles zero-dose children, nine reported coverage among this group of more than 50% (range: 12% and 91.6%). Conclusion: Even though a PCCS following an SIA is recommended and a requirement in Gavi-supported countries, most SIAs are not followed by a PCCS and, when performed, the timeliness of survey implementation needs improvement. Recent PCCSs were independently conducted and reports included basic survey information, but analysis and presentation of survey results vary particularly for measles zero-dose-related indicators. More guidance and technical support on how to implement PCCSs, including standardization of reports and more in-depth PCCS analyses, may help improve reporting and use of available PCCS data. Full article
(This article belongs to the Special Issue A World without Measles and Rubella: Meeting the Regional Elimination Targets on the Path to Global Eradication)
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17 pages, 2454 KB  
Review
Impact of Infections During Pregnancy on Transplacental Antibody Transfer
by Celeste Coler, Elana King-Nakaoka, Emma Every, Sophia Chima, Ashley Vong, Briana Del Rosario, Roslyn VanAbel and Kristina M. Adams Waldorf
Vaccines 2024, 12(10), 1199; https://doi.org/10.3390/vaccines12101199 - 21 Oct 2024
Cited by 11 | Viewed by 9146
Abstract
Vaccination in pregnancy is important to protect the mother and fetus from infectious diseases. The transfer of maternal antibodies across the placenta during pregnancy can continue to protect the neonate for several months after birth while the neonatal adaptive immune system develops. Several [...] Read more.
Vaccination in pregnancy is important to protect the mother and fetus from infectious diseases. The transfer of maternal antibodies across the placenta during pregnancy can continue to protect the neonate for several months after birth while the neonatal adaptive immune system develops. Several pathogens have been shown to impair the transplacental transfer of maternal antibodies, including human immunodeficiency virus, malaria, the severe acute respiratory syndrome coronavirus 2, and cytomegalovirus. This review discusses the mechanisms contributing to decreased transplacental antibody transfer in the setting of maternal infections, such as changes in antibody glycosylation profile, maternal hypergammaglobulinemia, and placental injury. The frequency of epidemics is increasing, and pregnant people are more likely to become exposed to novel pathogens now than they were in the past. Understanding the mechanisms by which infectious diseases impair maternal–fetal antibody transfer is important for pandemic preparedness to maximize the impact of maternal vaccination for child health. Full article
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16 pages, 1172 KB  
Review
T-Cell Epitope-Based Vaccines: A Promising Strategy for Prevention of Infectious Diseases
by Xin Song, Yongfeng Li, Hongxia Wu, Hua-Ji Qiu and Yuan Sun
Vaccines 2024, 12(10), 1181; https://doi.org/10.3390/vaccines12101181 - 17 Oct 2024
Cited by 29 | Viewed by 9365
Abstract
With the development of novel vaccine strategies, T-cell epitope-based vaccines have become promising prophylactic and therapeutic tools against infectious diseases that cannot be controlled via traditional vaccines. T-cell epitope-based vaccines leverage specific immunogenic peptides to elicit protective T-cell responses against infectious pathogens. Compared [...] Read more.
With the development of novel vaccine strategies, T-cell epitope-based vaccines have become promising prophylactic and therapeutic tools against infectious diseases that cannot be controlled via traditional vaccines. T-cell epitope-based vaccines leverage specific immunogenic peptides to elicit protective T-cell responses against infectious pathogens. Compared to traditional vaccines, they provide superior efficacy and safety, minimizing the risk of adverse side effects. In this review, we summarized and compared the prediction and identification methods of T-cell epitopes. By integrating bioinformatic prediction and experimental validation, efficient and precise screening of T-cell epitopes can be achieved. Importantly, we delved into the development approaches to diverse T-cell epitope-based vaccines, comparing their merits and demerits, as well as discussing the prevalent challenges and perspectives in their applications. This review offers fresh perspectives for the formulation of safe and efficacious epitope-based vaccines for the devastating diseases against which no vaccines are currently available. Full article
(This article belongs to the Special Issue Immunization Strategies for Animal Health)
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20 pages, 4599 KB  
Review
Recent Advances in Lipid Nanoparticles and Their Safety Concerns for mRNA Delivery
by Jialiang Wang, Yaopeng Ding, Kellie Chong, Meng Cui, Zeyu Cao, Chenjue Tang, Zhen Tian, Yuping Hu, Yu Zhao and Shaoyi Jiang
Vaccines 2024, 12(10), 1148; https://doi.org/10.3390/vaccines12101148 - 8 Oct 2024
Cited by 151 | Viewed by 27457
Abstract
Introduction: The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances in Therapeutic LNPs: LNPs, composed of ionizable lipids, phospholipids, cholesterol, and [...] Read more.
Introduction: The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances in Therapeutic LNPs: LNPs, composed of ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, facilitate efficient cellular uptake and cytosolic release of mRNA while mitigating degradation by nucleases. However, as synthetic entities, LNPs face challenges that alter their therapeutic efficacy and safety concerns. Toxicity/Reactogenicity/Immunogenicity: This review provides a comprehensive overview of the latest advancements in LNP research, focusing on preclinical safety assessments encompassing toxicity, reactogenicity, and immunogenicity. Summary and Outlook: Additionally, it outlines potential strategies for addressing these challenges and offers insights into future research directions for enhancing the application of LNPs in mRNA therapeutics. Full article
(This article belongs to the Special Issue Biotechnologies Applied in Vaccine Research)
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19 pages, 2943 KB  
Review
Ferritin Vaccine Platform for Animal and Zoonotic Viruses
by Sohrab Ahmadivand, Robert Fux and Dušan Palić
Vaccines 2024, 12(10), 1112; https://doi.org/10.3390/vaccines12101112 - 27 Sep 2024
Cited by 18 | Viewed by 6853
Abstract
Viral infections in animals continue to pose a significant challenge, affecting livestock health, welfare, and food safety, and, in the case of zoonotic viruses, threatening global public health. The control of viral diseases currently relies on conventional approaches such as inactivated or attenuated [...] Read more.
Viral infections in animals continue to pose a significant challenge, affecting livestock health, welfare, and food safety, and, in the case of zoonotic viruses, threatening global public health. The control of viral diseases currently relies on conventional approaches such as inactivated or attenuated vaccines produced via platforms with inherent limitations. Self-assembling ferritin nanocages represent a novel vaccine platform that has been utilized for several viruses, some of which are currently undergoing human clinical trials. Experimental evidence also supports the potential of this platform for developing commercial vaccines for veterinary viruses. In addition to improved stability and immunogenicity, ferritin-based vaccines are safe and DIVA-compatible, and can be rapidly deployed in response to emerging epidemics or pandemics. This review discusses the structural and functional properties of ferritin proteins, followed by an overview of the design and production of ferritin-based vaccines, the mechanisms of immune responses, and their applications in developing vaccines against animal and zoonotic viruses. Full article
(This article belongs to the Special Issue Vaccine Development for Emerging and Zoonotic Diseases)
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35 pages, 2230 KB  
Review
Navigating the Landscape of B Cell Mediated Immunity and Antibody Monitoring in SARS-CoV-2 Vaccine Efficacy: Tools, Strategies and Clinical Trial Insights
by Sophie O’Reilly, Joanne Byrne, Eoin R. Feeney, Patrick W. G. Mallon and Virginie Gautier
Vaccines 2024, 12(10), 1089; https://doi.org/10.3390/vaccines12101089 - 24 Sep 2024
Cited by 6 | Viewed by 4311
Abstract
Correlates of Protection (CoP) are biomarkers above a defined threshold that can replace clinical outcomes as primary endpoints, predicting vaccine effectiveness to support the approval of new vaccines or follow up studies. In the context of COVID-19 vaccination, CoPs can help address challenges [...] Read more.
Correlates of Protection (CoP) are biomarkers above a defined threshold that can replace clinical outcomes as primary endpoints, predicting vaccine effectiveness to support the approval of new vaccines or follow up studies. In the context of COVID-19 vaccination, CoPs can help address challenges such as demonstrating vaccine effectiveness in special populations, against emerging SARS-CoV-2 variants or determining the durability of vaccine-elicited immunity. While anti-spike IgG titres and viral neutralising capacity have been characterised as CoPs for COVID-19 vaccination, the contribution of other components of the humoral immune response to immediate and long-term protective immunity is less well characterised. This review examines the evidence supporting the use of CoPs in COVID-19 clinical vaccine trials, and how they can be used to define a protective threshold of immunity. It also highlights alternative humoral immune biomarkers, including Fc effector function, mucosal immunity, and the generation of long-lived plasma and memory B cells and discuss how these can be applied to clinical studies and the tools available to study them. Full article
(This article belongs to the Special Issue Immune Effectiveness of COVID-19 Vaccines)
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17 pages, 616 KB  
Review
Hybrid Immunity against SARS-CoV-2 Variants: A Narrative Review of the Literature
by Panagiota Tsagkli, Maria Geropeppa, Ioanna Papadatou and Vana Spoulou
Vaccines 2024, 12(9), 1051; https://doi.org/10.3390/vaccines12091051 - 14 Sep 2024
Cited by 14 | Viewed by 10187
Abstract
The emergence of SARS-CoV-2 led to a global health crisis and the burden of the disease continues to persist. The rapid development and emergency authorization of various vaccines, including mRNA-based vaccines, played a pivotal role in mitigating severe illness and mortality. However, rapid [...] Read more.
The emergence of SARS-CoV-2 led to a global health crisis and the burden of the disease continues to persist. The rapid development and emergency authorization of various vaccines, including mRNA-based vaccines, played a pivotal role in mitigating severe illness and mortality. However, rapid viral mutations, leading to several variants of concern, challenged vaccine effectiveness, particularly concerning immune evasion. Research on immunity, both from natural infection and vaccination, revealed that while neutralizing antibodies provide protection against infection, their effect is short-lived. The primary defense against severe COVID-19 is derived from the cellular immune response. Hybrid immunity, developed from a combination of natural infection and vaccination, offers enhanced protection, with convalescent vaccinated individuals showing significantly higher levels of neutralizing antibodies. As SARS-CoV-2 continues to evolve, understanding the durability and breadth of hybrid immunity becomes crucial. This narrative review examines the latest data on humoral and cellular immunity from both natural infection and vaccination, discussing how hybrid immunity could inform and optimize future vaccination strategies in the ongoing battle against COVID-19 and in fear of a new pandemic. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)
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18 pages, 319 KB  
Review
HIV Vaccine Development at a Crossroads: New B and T Cell Approaches
by Ramesh Govindan and Kathryn E. Stephenson
Vaccines 2024, 12(9), 1043; https://doi.org/10.3390/vaccines12091043 - 12 Sep 2024
Cited by 11 | Viewed by 9163
Abstract
Despite rigorous scientific efforts over the forty years since the onset of the global HIV pandemic, a safe and effective HIV-1 vaccine remains elusive. The challenges of HIV vaccine development have proven immense, in large part due to the tremendous sequence diversity of [...] Read more.
Despite rigorous scientific efforts over the forty years since the onset of the global HIV pandemic, a safe and effective HIV-1 vaccine remains elusive. The challenges of HIV vaccine development have proven immense, in large part due to the tremendous sequence diversity of HIV and its ability to escape from antiviral adaptive immune responses. In recent years, several phase 3 efficacy trials have been conducted, testing a similar hypothesis, e.g., that non-neutralizing antibodies and classical cellular immune responses could prevent HIV-1 acquisition. These studies were not successful. As a result, the field has now pivoted to bold novel approaches, including sequential immunization strategies to drive the generation of broadly neutralizing antibodies and human CMV-vectored vaccines to elicit MHC-E-restricted CD8+ T cell responses. Many of these vaccine candidates are now in phase 1 trials, with early promising results. Full article
(This article belongs to the Special Issue T-cell Immunity and Viral Pathogenicity on Vaccine Efficacy)
21 pages, 3794 KB  
Review
The Major Role of T Regulatory Cells in the Efficiency of Vaccination in General and Immunocompromised Populations: A Review
by Stanislaw Stepkowski, Dulat Bekbolsynov, Jared Oenick, Surina Brar, Beata Mierzejewska, Michael A. Rees and Obi Ekwenna
Vaccines 2024, 12(9), 992; https://doi.org/10.3390/vaccines12090992 - 30 Aug 2024
Cited by 6 | Viewed by 4765
Abstract
Since their conception with the smallpox vaccine, vaccines used worldwide have mitigated multiple pandemics, including the recent COVID-19 outbreak. Insightful studies have uncovered the complexities of different functional networks of CD4 T cells (T helper 1 (Th1); Th2, Th17) and CD8 T cells [...] Read more.
Since their conception with the smallpox vaccine, vaccines used worldwide have mitigated multiple pandemics, including the recent COVID-19 outbreak. Insightful studies have uncovered the complexities of different functional networks of CD4 T cells (T helper 1 (Th1); Th2, Th17) and CD8 T cells (T cytotoxic; Tc), as well as B cell (BIgM, BIgG, BIgA and BIgE) subsets, during the response to vaccination. Both T and B cell subsets form central, peripheral, and tissue-resident subsets during vaccination. It has also become apparent that each vaccination forms a network of T regulatory subsets, namely CD4+ CD25+ Foxp3+ T regulatory (Treg) cells and interleukin-10 (IL-10)-producing CD4+ Foxp3− T regulatory 1 (Tr1), as well as many others, which shape the quality/quantity of vaccine-specific IgM, IgG, and IgA antibody production. These components are especially critical for immunocompromised patients, such as older individuals and allograft recipients, as their vaccination may be ineffective or less effective. This review focuses on considering how the pre- and post-vaccination Treg/Tr1 levels influence the vaccination efficacy. Experimental and clinical work has revealed that Treg/Tr1 involvement evokes different immune mechanisms in diminishing vaccine-induced cellular/humoral responses. Alternative steps may be considered to improve the vaccination response, such as increasing the dose, changing the delivery route, and/or repeated booster doses of vaccines. Vaccination may be combined with anti-CD25 (IL-2Rα chain) or anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAb) to decrease the Tregs and boost the T/B cell immune response. All of these data and strategies for immunizations are presented and discussed, aiming to improve the efficacy of vaccination in humans and especially in immunocompromised and older individuals, as well as organ transplant patients. Full article
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14 pages, 3226 KB  
Article
Immunogenicity and Protective Efficacy of a Multi-Antigen Mycobacterium tuberculosis Subunit Vaccine in Mice
by Annuurun Nisa, Rachel Pinto, Warwick J. Britton, James A. Triccas and Claudio Counoupas
Vaccines 2024, 12(9), 997; https://doi.org/10.3390/vaccines12090997 - 30 Aug 2024
Cited by 4 | Viewed by 7279
Abstract
There is an urgent need for an effective TB vaccine capable of controlling both acute and chronic Mycobacterium tuberculosis infection in populations with diverse genetic backgrounds. In this study, we characterised the immunogenicity and protective efficacy of a novel protein-in-adjuvant subunit vaccine. The [...] Read more.
There is an urgent need for an effective TB vaccine capable of controlling both acute and chronic Mycobacterium tuberculosis infection in populations with diverse genetic backgrounds. In this study, we characterised the immunogenicity and protective efficacy of a novel protein-in-adjuvant subunit vaccine. The protein component is a fusion protein of three different M. tuberculosis antigens, which we termed CysVac5: CysD, a major component of the M. tuberculosis sulfate activation pathway that is highly expressed during the chronic stage of M. tuberculosis infection, is fused with two major secreted mycobacterial antigens, Ag85B and MPT83. Vaccination of C57BL/6 mice with CysVac5, formulated in a monophosphoryl lipid A (MPLA) and dimethyldioctadecylammonium (DDA) adjuvant combination, resulted in the potent generation of polyfunctional CD4+ T cells secreting multiple cytokines, including IFN-γ, IL-2, TNF and IL-17, against each of the three components of the fusion protein. Furthermore, vaccination with CysVac5-MPLA/DDA conferred significant protection against infection in mouse lungs, which was greater than that afforded by BCG at extended time points post-challenge. The generation of antigen-specific and protective immunity was also observed in CysVac5 vaccinated BALB/c mice, indicating the vaccine could display efficacy across multiple genetic backgrounds. These results indicate that the CysVac5 vaccine has broad immunogenicity, is effective in controlling both acute and chronic phases of M. tuberculosis infection in mice, and warrants further investigation to assess its potential to control pulmonary TB. Full article
(This article belongs to the Special Issue Tuberculosis Vaccines and Host-Directed Therapies)
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12 pages, 940 KB  
Article
The Influence of SARS-CoV-2 Vaccination on the Mortality and Outcomes of Patients with Both Myocardial Infarction and COVID-19
by Eugeniusz Hrycek, Anna Walawska-Hrycek, Krzysztof Milewski, Przemysław Nowakowski, Piotr Buszman and Aleksander Żurakowski
Vaccines 2024, 12(9), 983; https://doi.org/10.3390/vaccines12090983 - 29 Aug 2024
Cited by 3 | Viewed by 4656
Abstract
Background: This multi-site retrospective analysis with a control group was devised to evaluate the impact of prophylactic SARS-CoV-2 vaccination the on outcomes of myocardial infarction (MI) patients with confirmed COVID-19. Methods: An overall of 129 subjects who had been diagnosed with COVID-19 and [...] Read more.
Background: This multi-site retrospective analysis with a control group was devised to evaluate the impact of prophylactic SARS-CoV-2 vaccination the on outcomes of myocardial infarction (MI) patients with confirmed COVID-19. Methods: An overall of 129 subjects who had been diagnosed with COVID-19 and MI were included in the analysis and were divided into the study group (44 vaccinated patients) and the control group (85 non-vaccinated comparable patients). The primary outcome measure was defined as the time until in-hospital death, while the secondary outcome measure was defined as the time until death outside the hospital setting. Results: According to in-hospital mortality analysis, 1 (2.27%) subject died in the study group, whereas a total of 19 (22.4%) subjects died among the controls (OR = 0.08; CI: 0.001–0.553; p = 0.023). The impact of vaccination on the in-hospital outcomes of patients treated for COVID-19 and MI was further confirmed using Cox regression analysis (HR: 0.1 CI: 0.01–0.77; p = 0.026). The observed difference was the absence of respiratory failure requiring mechanical ventilation in the study group, whereas it was observed in 14 (16.47%) patients in the control group. During out-of-hospital observation, there were no observed differences in mortality (OR: 1.56; 95% CI: 0.21–11.52; p = 0.66). Conclusions: The complete prophylactic SARS-CoV-2 vaccination course demonstrates a protective role in patients undergoing treatment for MI with confirmed COVID-19 during in-hospital observation. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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